Is GANAB p.Val76Phe (c.226G>T) pathogenic?

GANAB p.Val76Phe (c.226G>T) is classified Uncertain significance in GANAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-20). AlphaMissense: likely benign (0.3022); Very rare (popmax 0.00334%, amr).

How common is GANAB p.Val76Phe (c.226G>T) in the general population?

GANAB p.Val76Phe (c.226G>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about GANAB p.Val76Phe (c.226G>T)?

AlphaMissense predicts likely benign (score 0.3022) — an in-silico prediction, not a clinical call.

GANAB p.Val76Phe

c.226G>T · rs1384463982 · VCV1909662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3022	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 2.5, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.65 · regional, not allelic
Overall
CADD	16.13	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 0.00334% Admixed American · 2/59,906 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,611,632 alleles · very rare exomes 1/1,459,842 · genomes 1/151,790 · 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: GANAB
Protein: p.Val76Phe
Coding: c.226G>T
MANE Select: NM_198334
dbSNP: rs1384463982
Type: single nucleotide variant
Location: chr11:62639385 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB
Residue 76: a β-strand

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

Similar variants

GANAB p.Val76= Likely benign ★ same residue
GANAB p.Arg112Ter Likely pathogenic ★★ same type
GANAB p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Arg61Ter Pathogenic ★★ same type
GANAB p.Arg812Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Arg815Ter Pathogenic/Likely pathogenic ★★ same type
GANAB p.Arg817Trp Likely pathogenic ★★ same type
GANAB p.Gln414Ter Pathogenic/Likely pathogenic ★★ 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/ganab-p-val76phe (accessed [today's date]).

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