Is GAP43 p.Ser151Leu (c.452C>T) pathogenic?

GAP43 p.Ser151Leu (c.452C>T) is classified Uncertain significance in GAP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0583); Ultra-rare (popmax 0.0164%, mid).

How common is GAP43 p.Ser151Leu (c.452C>T) in the general population?

GAP43 p.Ser151Leu (c.452C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about GAP43 p.Ser151Leu (c.452C>T)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

GAP43 p.Ser151Leu

c.452C>T · VCV4261764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.52, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 97 kb · p 0.84 · regional, not allelic
Overall
CADD	19.91	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000991% 16/1,613,834 alleles · ultra-rare exomes 12/1,461,690 · genomes 4/152,144 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00935%	10,701
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asian	0.00223%	44,884
European (non-Finnish)	0.00017%	589,960

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.Ser151Leu
Coding: c.452C>T
MANE Select: NM_002045
Type: single nucleotide variant
Location: chr3:115676434 (GRCh38)
Gene constraint: LOEUF 0.358 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.00
Residue 151: a modified residue (phosphoserine); 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-ser151leu (accessed [today's date]).

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