Is GPAA1 p.Pro571Ser (c.1711C>T) pathogenic?

GPAA1 p.Pro571Ser (c.1711C>T) is classified Uncertain significance in GPAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: likely benign (0.1482); Rare (popmax 0.121%, sas).

How common is GPAA1 p.Pro571Ser (c.1711C>T) in the general population?

GPAA1 p.Pro571Ser (c.1711C>T) is rare (popmax 0.121%, sas) (gnomAD).

What do computational predictors say about GPAA1 p.Pro571Ser (c.1711C>T)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

GPAA1 p.Pro571Ser

c.1711C>T · rs564194070 · VCV1411613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 3,391 bp · p 0.14 · regional, not allelic
Overall
CADD	25.2	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 0.121% South Asian · 110/91,078 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0956%

Overall 0.00709% 114/1,606,856 alleles · rare exomes 105/1,454,570 · genomes 9/152,286 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.121%	828
Remaining individualsnot grpmax-eligible	0.0048%	20,818
African / African-American	0.00133%	75,048

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.Pro571Ser
Coding: c.1711C>T
MANE Select: NM_003801
dbSNP: rs564194070
Type: single nucleotide variant
Location: chr8:144085970 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.48 · 4 PDB

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-pro571ser (accessed [today's date]).

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