Is PGAP3 p.Val211Asp (c.632T>A) pathogenic?

PGAP3 p.Val211Asp (c.632T>A) is classified Uncertain significance in PGAP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-16). AlphaMissense: likely pathogenic (0.9582); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PGAP3 p.Val211Asp (c.632T>A)?

PGAP3 p.Val211Asp (c.632T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP3 p.Val211Asp (c.632T>A) in the general population?

PGAP3 p.Val211Asp (c.632T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAP3 p.Val211Asp (c.632T>A)?

AlphaMissense predicts likely pathogenic (score 0.9582) — an in-silico prediction, not a clinical call.

PGAP3 p.Val211Asp

c.632T>A · VCV3696872

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9582 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9582	likely pathogenic · top 9% in PGAP3
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -14.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.63 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PGAP3
Protein: p.Val211Asp
Coding: c.632T>A
MANE Select: NM_033419
Type: single nucleotide variant
Location: chr17:39673576 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PGAP3 p.Val211Ile Likely benign ★ same residue
PER1 p.Glu211Asp Uncertain significance ★ ⚠ same residue
PGAP3 p.Glu37Ter Pathogenic ★★ same condition
PGAP3 p.Arg126Cys Uncertain significance ★★ ⚠ same condition
PGAP3 p.Gly84Asp Uncertain significance ★★ ⚠ same condition
PGAP3 p.Thr161Ile Uncertain significance ★★ same condition
PGAP3 p.Val145Ala Uncertain significance ★★ same condition
PGAP3 p.Val253Met Uncertain significance ★★ ⚠ same condition

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-val211asp (accessed [today's date]).

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