Is GPC3 p.Ala232Asp (c.695C>A) pathogenic?

GPC3 p.Ala232Asp (c.695C>A) is classified Likely pathogenic in GPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-10). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1; Associated with Simpson-Golabi-Behmel syndrome type 1.

What condition is associated with GPC3 p.Ala232Asp (c.695C>A)?

GPC3 p.Ala232Asp (c.695C>A) is associated with Simpson-Golabi-Behmel syndrome type 1 (ClinVar).

How common is GPC3 p.Ala232Asp (c.695C>A) in the general population?

GPC3 p.Ala232Asp (c.695C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPC3 p.Ala232Asp (c.695C>A)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

GPC3 p.Ala232Asp

c.695C>A · rs1206002281 · VCV1699090

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Simpson-Golabi-Behmel syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic ✓ concordant with ClinVar · top 2% in GPC3
REVEL	0.764	pathogenic-leaning
SaProt	LLR -13.88	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 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 449 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	29.0	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

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: GPC3
Protein: p.Ala232Asp
Coding: c.695C>A
MANE Select: NM_004484
dbSNP: rs1206002281
Type: single nucleotide variant
Location: chrX:133753819 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 232: an α-helix

Full GPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Simpson-Golabi-Behmel syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GPC3 p.Ala232= Likely benign ★★ same residue
GPC3 p.Ala232Val Uncertain significance ★ ⚠ same residue
GPC3 p.Arg199Ter Pathogenic ★★ same condition
GPC3 p.Arg387Ter Pathogenic ★★ same condition
GPC3 p.Gly556Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
GPC3 c.1292+6C>T Uncertain significance ★★ same condition
GPC3 p.Ala338Thr Uncertain significance ★★ ⚠ same condition
GPC3 p.Arg39Cys Uncertain significance ★★ ⚠ 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/gpc3-p-ala232asp (accessed [today's date]).

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