Is SEC23B p.Arg313His (c.938G>A) pathogenic?

SEC23B p.Arg313His (c.938G>A) is classified Pathogenic/Likely pathogenic in SEC23B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-01). AlphaMissense: likely pathogenic (0.9753); Very rare (popmax 0.00167%, amr); Associated with congenital dyserythropoietic anemia type 2.

What condition is associated with SEC23B p.Arg313His (c.938G>A)?

SEC23B p.Arg313His (c.938G>A) is associated with congenital dyserythropoietic anemia type 2, Cowden syndrome 7 (ClinVar).

How common is SEC23B p.Arg313His (c.938G>A) in the general population?

SEC23B p.Arg313His (c.938G>A) is very rare (popmax 0.00167%, amr) (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.Arg313His (c.938G>A)?

AlphaMissense predicts likely pathogenic (score 0.9753) — an in-silico prediction, not a clinical call.

SEC23B p.Arg313His

c.938G>A · rs750888081 · VCV2925647

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type 2

Computational evidence

Protein change
AlphaMissense	0.9753	likely pathogenic ✓ concordant with ClinVar
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -14.23	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 50 kb · p 0.036 · regional, not allelic
Overall
CADD	33.0	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 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,136 alleles · very rare exomes 4/1,461,886 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,005

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.Arg313His
Coding: c.938G>A
MANE Select: NM_006363
dbSNP: rs750888081
Type: single nucleotide variant
Location: chr20:18526476 (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.Arg313Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg313his (accessed [today's date]).

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