Is SEC23B p.Ala68Thr (c.202G>A) pathogenic?

SEC23B p.Ala68Thr (c.202G>A) is classified Uncertain significance in SEC23B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-17). AlphaMissense: likely pathogenic (0.8696); Absent from gnomAD v4.1; Associated with Cowden syndrome 7.

What condition is associated with SEC23B p.Ala68Thr (c.202G>A)?

SEC23B p.Ala68Thr (c.202G>A) is associated with Cowden syndrome 7, congenital dyserythropoietic anemia type 2 (ClinVar).

How common is SEC23B p.Ala68Thr (c.202G>A) in the general population?

SEC23B p.Ala68Thr (c.202G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SEC23B p.Ala68Thr (c.202G>A)?

AlphaMissense predicts likely pathogenic (score 0.8696) — an in-silico prediction, not a clinical call.

SEC23B p.Ala68Thr

c.202G>A · rs2059977778 · VCV897909

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8696 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cowden syndrome 7

Computational evidence

Protein change
AlphaMissense	0.8696	likely pathogenic
REVEL	0.771	pathogenic-leaning
SaProt	LLR -12.68	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	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SEC23B
Protein: p.Ala68Thr
Coding: c.202G>A
MANE Select: NM_006363
dbSNP: rs2059977778
Type: single nucleotide variant
Location: chr20:18511037 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.41

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

Disease context

Cowden syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital dyserythropoietic anemia type 2

Similar variants

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.Arg313His Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg324Ter Pathogenic/Likely pathogenic ★★ same condition
SEC23B p.Arg339Ter 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-ala68thr (accessed [today's date]).

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