Is GPAA1 p.Ser210Phe (c.629C>T) pathogenic?

GPAA1 p.Ser210Phe (c.629C>T) is classified Benign/Likely benign in GPAA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1693); Low-frequency (popmax 1.36%, afr).

How common is GPAA1 p.Ser210Phe (c.629C>T) in the general population?

GPAA1 p.Ser210Phe (c.629C>T) is low-frequency (popmax 1.36%, afr) (gnomAD).

What do computational predictors say about GPAA1 p.Ser210Phe (c.629C>T)?

AlphaMissense predicts likely benign (score 0.1693) — an in-silico prediction, not a clinical call.

GPAA1 p.Ser210Phe

c.629C>T · rs73379188 · VCV716091

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1693 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.36%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1693	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 0.61, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 3,391 bp · p 0.14 · regional, not allelic
Overall
CADD	23.9	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 1.36% African / African-American · 1,021/74,998 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.0682% 1,101/1,613,490 alleles · low-frequency exomes 527/1,461,248 · genomes 574/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.36%	73
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.0466%	2,144
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.0011%	90,763
South Asian	0.0011%	91,078

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: GPAA1
Protein: p.Ser210Phe
Coding: c.629C>T
MANE Select: NM_003801
dbSNP: rs73379188
Type: single nucleotide variant
Location: chr8:144084146 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.48 · 4 PDB
Residue 210: an α-helix

Full GPAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPAA1 c.1165-1C>T Likely pathogenic ★★ same type
GPAA1 c.366+1G>A Likely pathogenic ★★ same type
GPAA1 c.616+1G>T Likely pathogenic ★★ same type
GPAA1 p.Arg215Ter Pathogenic/Likely pathogenic ★★ same type
GPAA1 p.Leu291Pro Likely pathogenic ★★ same type
GPAA1 p.Ser419Ter Pathogenic/Likely pathogenic ★★ same type
GPAA1 c.1164+1A>G Uncertain significance ★★ same type
GPAA1 c.1451+5G>A 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/gpaa1-p-ser210phe (accessed [today's date]).

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