Is GAP43 p.Ala62Pro (c.184G>C) pathogenic?

GAP43 p.Ala62Pro (c.184G>C) is classified Uncertain significance in GAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.1598); Ultra-rare (popmax 0.0395%, sas).

How common is GAP43 p.Ala62Pro (c.184G>C) in the general population?

GAP43 p.Ala62Pro (c.184G>C) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

What do computational predictors say about GAP43 p.Ala62Pro (c.184G>C)?

AlphaMissense predicts likely benign (score 0.1598) — an in-silico prediction, not a clinical call.

GAP43 p.Ala62Pro

c.184G>C · rs777937866 · VCV2404275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1598 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1598	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 97 kb · p 0.84 · regional, not allelic
Overall
CADD	23.0	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 0.0395% South Asian · 36/91,080 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00248% 40/1,614,082 alleles · ultra-rare exomes 39/1,461,894 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	8.47e-05%	1,180,038

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.Ala62Pro
Coding: c.184G>C
MANE Select: NM_002045
dbSNP: rs777937866
Type: single nucleotide variant
Location: chr3:115676166 (GRCh38)
Gene constraint: LOEUF 0.358 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.00
Residue 62: 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-ala62pro (accessed [today's date]).

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