Is PGAP3 p.Val260Ala (c.779T>C) pathogenic?

PGAP3 p.Val260Ala (c.779T>C) is classified Uncertain significance in PGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: ambiguous (0.3789); Very rare (popmax 0.000257%, nfe).

How common is PGAP3 p.Val260Ala (c.779T>C) in the general population?

PGAP3 p.Val260Ala (c.779T>C) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about PGAP3 p.Val260Ala (c.779T>C)?

AlphaMissense predicts ambiguous (score 0.3789) — an in-silico prediction, not a clinical call.

PGAP3 p.Val260Ala

c.779T>C · rs1248974263 · VCV1933184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3789	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -11.38	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor loss, 14 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.63 · regional, not allelic
Overall
CADD	24.4	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 0.000257% European (non-Finnish) · 3/1,167,016 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000189% 3/1,586,454 alleles · very rare exomes 3/1,434,268 · genomes 0/152,186 · 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: PGAP3
Protein: p.Val260Ala
Coding: c.779T>C
MANE Select: NM_033419
dbSNP: rs1248974263
Type: single nucleotide variant
Location: chr17:39673171 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.17

Full PGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAP3 p.Val260del Uncertain significance ★ same residue
PGAP3 c.558-10G>A Pathogenic/Likely pathogenic ★★ same type
PGAP3 c.694+1G>A Pathogenic ★★ same type
PGAP3 p.Asp305Gly Pathogenic/Likely pathogenic ★★ same type
PGAP3 p.Gln89Ter Pathogenic ★★ same type
PGAP3 p.Glu37Ter Pathogenic ★★ same type
PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
PGAP3 p.His284Tyr Pathogenic/Likely pathogenic ★★ 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/pgap3-p-val260ala (accessed [today's date]).

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