Is SEC23B p.Arg313Cys (c.937C>T) pathogenic?

SEC23B p.Arg313Cys (c.937C>T) is classified Conflicting classifications of pathogenicity in SEC23B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-05-24). AlphaMissense: likely pathogenic (0.965); Very rare (popmax 0.00144%, nfe); Associated with congenital dyserythropoietic anemia type 2.

What condition is associated with SEC23B p.Arg313Cys (c.937C>T)?

SEC23B p.Arg313Cys (c.937C>T) is associated with congenital dyserythropoietic anemia type 2, Cowden syndrome 7 (ClinVar).

How common is SEC23B p.Arg313Cys (c.937C>T) in the general population?

SEC23B p.Arg313Cys (c.937C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

How is Congenital dyserythropoietic anemia type II inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SEC23B p.Arg313Cys (c.937C>T)?

AlphaMissense predicts likely pathogenic (score 0.965) — an in-silico prediction, not a clinical call.

SEC23B p.Arg313Cys

c.937C>T · rs111758941 · VCV2920946

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type 2

Computational evidence

Protein change
AlphaMissense	0.965	likely pathogenic
REVEL	0.871	moderately pathogenic-leaning
SaProt	LLR -13.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 50 kb · p 0.036 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,006 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,614,006 alleles · very rare exomes 17/1,461,876 · genomes 1/152,130 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.00144%	69,412

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SEC23B
Protein: p.Arg313Cys
Coding: c.937C>T
MANE Select: NM_006363
dbSNP: rs111758941
Type: single nucleotide variant
Location: chr20:18526475 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.41
Residue 313: a UniProt-annotated variant site (in)

Full SEC23B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital dyserythropoietic anemia type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cowden syndrome 7

For Congenital dyserythropoietic anemia type II (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

SEC23B p.Arg313His Pathogenic/Likely pathogenic ★★ same residue
SEC23B p.Arg313Leu Uncertain significance ★ ⚠ same residue
SEC23B c.1314+1G>A Likely pathogenic ★★ same condition
SEC23B c.835-2A>G Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Ala524Val Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg14Trp Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg264Ter Pathogenic ★★ same condition
SEC23B p.Arg324Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sec23b-p-arg313cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown