Is PGAP1 p.Val15Ala (c.44T>C) pathogenic?

PGAP1 p.Val15Ala (c.44T>C) is classified Uncertain significance in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-05). AlphaMissense: likely benign (0.0765); Very rare (popmax 0.00517%, nfe).

How common is PGAP1 p.Val15Ala (c.44T>C) in the general population?

PGAP1 p.Val15Ala (c.44T>C) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about PGAP1 p.Val15Ala (c.44T>C)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

PGAP1 p.Val15Ala

c.44T>C · rs373419311 · VCV1336722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	13.96	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 0.00517% European (non-Finnish) · 61/1,180,006 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.0039% 63/1,614,002 alleles · very rare exomes 60/1,461,868 · genomes 3/152,134 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,344
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,918

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: PGAP1
Protein: p.Val15Ala
Coding: c.44T>C
MANE Select: NM_024989
dbSNP: rs373419311
Type: single nucleotide variant
Location: chr2:196926573 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.15

Full PGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAP1 p.Val15Ile Uncertain significance ★★ ⚠ same residue
PGAP1 p.Arg231Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Gln466Ter Pathogenic ★★ same type
PGAP1 p.Gln555Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Tyr758Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same type
PGAP1 p.Ala714Val Uncertain significance ★★ ⚠ same type
PGAP1 p.Ala864Val 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/pgap1-p-val15ala (accessed [today's date]).

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