Is SEC23A p.Cys61Tyr (c.182G>A) pathogenic?

SEC23A p.Cys61Tyr (c.182G>A) is classified Uncertain significance in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is SEC23A p.Cys61Tyr (c.182G>A) in the general population?

SEC23A p.Cys61Tyr (c.182G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SEC23A p.Cys61Tyr (c.182G>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

SEC23A p.Cys61Tyr

c.182G>A · VCV3951734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 2% in SEC23A
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -13.07	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 7.6	GERP 1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 0.001 · regional, not allelic
Overall
CADD	32.0	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: SEC23A
Protein: p.Cys61Tyr
Coding: c.182G>A
MANE Select: NM_006364
Type: single nucleotide variant
Location: chr14:39095937 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB
Residue 61: a binding site

Full SEC23A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC23A p.Ala284Pro Uncertain significance ★★ ⚠ same type
SEC23A p.Ala478Ser Uncertain significance ★★ ⚠ same type
SEC23A p.Arg123Cys Uncertain significance ★★ ⚠ same type
SEC23A p.Arg476His Uncertain significance ★★ ⚠ same type
SEC23A p.Arg67His Uncertain significance ★★ ⚠ same type
SEC23A p.Arg716Cys Uncertain significance ★★ ⚠ same type
SEC23A p.Asn680Asp Uncertain significance ★★ ⚠ same type
SEC23A p.Cys180Tyr Uncertain significance ★★ ⚠ same type

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/sec23a-p-cys61tyr (accessed [today's date]).

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