Is GAP43 p.Val74= (c.222T>C) pathogenic?

GAP43 p.Val74= (c.222T>C) is classified Likely benign in GAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Ultra-rare (popmax 0.0111%, eas).

How common is GAP43 p.Val74= (c.222T>C) in the general population?

GAP43 p.Val74= (c.222T>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

GAP43 p.Val74=

c.222T>C · rs762538944 · VCV3098306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.7	GERP -5.2
Overall
CADD	0.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,876 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,990 alleles · ultra-rare exomes 4/1,461,894 · genomes 1/152,096 · joint denominator

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.Val74=
Coding: c.222T>C
MANE Select: NM_002045
dbSNP: rs762538944
Type: single nucleotide variant
Location: chr3:115676204 (GRCh38)
Gene constraint: LOEUF 0.358 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.00
Residue 74: 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-val74 (accessed [today's date]).

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