Is GOLGA3 p.Ser123Phe (c.368C>T) pathogenic?

GOLGA3 p.Ser123Phe (c.368C>T) is classified Uncertain significance in GOLGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.6894); Very rare (popmax 0.000169%, nfe).

How common is GOLGA3 p.Ser123Phe (c.368C>T) in the general population?

GOLGA3 p.Ser123Phe (c.368C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about GOLGA3 p.Ser123Phe (c.368C>T)?

AlphaMissense predicts likely pathogenic (score 0.6894) — an in-silico prediction, not a clinical call.

GOLGA3 p.Ser123Phe

c.368C>T · rs780845796 · VCV3100760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6894	likely pathogenic
REVEL	0.36	indeterminate
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 49 kb · p 0.48 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,980 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,068 alleles · very rare exomes 2/1,461,680 · genomes 0/152,388 · 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: GOLGA3
Protein: p.Ser123Phe
Coding: c.368C>T
MANE Select: NM_001389683
dbSNP: rs780845796
Type: single nucleotide variant
Location: chr12:132816578 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 123: the 'interaction with gopc' 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-ser123phe (accessed [today's date]).

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