Is GOLGA3 p.Val43Phe (c.127G>T) pathogenic?

GOLGA3 p.Val43Phe (c.127G>T) is classified Uncertain significance in GOLGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.00404%, afr).

How common is GOLGA3 p.Val43Phe (c.127G>T) in the general population?

GOLGA3 p.Val43Phe (c.127G>T) is very rare (popmax 0.00404%, afr) (gnomAD).

What do computational predictors say about GOLGA3 p.Val43Phe (c.127G>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

GOLGA3 p.Val43Phe

c.127G>T · rs769252763 · VCV2271510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.40	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 1.6	GERP 1.3, phastCons 0.14
Regional constraint	o/e 0.98	unconstrained · MANE · 49 kb · p 0.48 · regional, not allelic
Overall
CADD	15.82	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 0.00404% African / African-American · 3/74,192 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000832%

Overall 0.00143% 23/1,606,006 alleles · very rare exomes 18/1,453,870 · genomes 5/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,731
European (non-Finnish)	0.00161%	61,927
South Asian	0.00111%	90,480

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: GOLGA3
Protein: p.Val43Phe
Coding: c.127G>T
MANE Select: NM_001389683
dbSNP: rs769252763
Type: single nucleotide variant
Location: chr12:132822002 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 43: the 'disordered' region

Full GOLGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GOLGA3 p.Ala563Val Benign ★★ same type
GOLGA3 c.2812-1G>A Uncertain significance ★ same type
GOLGA3 p.Ala1015Val Uncertain significance ★ ⚠ same type
GOLGA3 p.Ala1019Pro Uncertain significance ★ ⚠ same type
GOLGA3 p.Ala1019Thr Uncertain significance ★ ⚠ same type
GOLGA3 p.Ala1022Thr Uncertain significance ★ ⚠ same type
GOLGA3 p.Ala1029Val Uncertain significance ★ ⚠ same type
GOLGA3 p.Ala1070Val 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/golga3-p-val43phe (accessed [today's date]).

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