Is GOLGA3 p.Ala784Val (c.2351C>T) pathogenic?

GOLGA3 p.Ala784Val (c.2351C>T) is classified Uncertain significance in GOLGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1283); Very rare (popmax 0.00891%, eas).

How common is GOLGA3 p.Ala784Val (c.2351C>T) in the general population?

GOLGA3 p.Ala784Val (c.2351C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about GOLGA3 p.Ala784Val (c.2351C>T)?

AlphaMissense predicts likely benign (score 0.1283) — an in-silico prediction, not a clinical call.

GOLGA3 p.Ala784Val

c.2351C>T · VCV3854604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1283	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.88	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 6.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 49 kb · p 0.48 · regional, not allelic
Overall
CADD	20.5	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 0.00891% East Asian · 4/44,874 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000806% 13/1,613,708 alleles · very rare exomes 11/1,461,502 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
Remaining individualsnot grpmax-eligible	0.0016%	62,500
African / African-American	0.00133%	75,010
South Asian	0.0011%	91,066
European (non-Finnish)	0.000508%	196,667

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.Ala784Val
Coding: c.2351C>T
MANE Select: NM_001389683
Type: single nucleotide variant
Location: chr12:132795970 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76

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-ala784val (accessed [today's date]).

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