Is GAP43 p.Ala211Ser (c.631G>T) pathogenic?

GAP43 p.Ala211Ser (c.631G>T) is classified Uncertain significance in GAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1185); Ultra-rare (popmax 0.0117%, amr).

How common is GAP43 p.Ala211Ser (c.631G>T) in the general population?

GAP43 p.Ala211Ser (c.631G>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about GAP43 p.Ala211Ser (c.631G>T)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

GAP43 p.Ala211Ser

c.631G>T · VCV4261765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.70	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 97 kb · p 0.84 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0117% Admixed American · 7/59,838 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000497% 8/1,610,870 alleles · ultra-rare exomes 8/1,458,724 · genomes 0/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,548
Remaining individualsnot grpmax-eligible	0.0016%	62,348

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: GAP43
Protein: p.Ala211Ser
Coding: c.631G>T
MANE Select: NM_002045
Type: single nucleotide variant
Location: chr3:115720796 (GRCh38)
Gene constraint: LOEUF 0.358 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.00
Residue 211: the 'disordered' region

Full GAP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GAP43 c.31-12223C>T Benign ★★ same type
GAP43 c.31-12167G>A Uncertain significance ★ same type
GAP43 c.31-12204C>T Uncertain significance ★ same type
GAP43 p.Ala124Gly Uncertain significance ★ ⚠ same type
GAP43 p.Ala135Ser Uncertain significance ★ ⚠ same type
GAP43 p.Ala135Thr Uncertain significance ★ ⚠ same type
GAP43 p.Ala146Ser Uncertain significance ★ ⚠ same type
GAP43 p.Ala178Ser 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/gap43-p-ala211ser (accessed [today's date]).

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