Is PGAP1 p.Ala714Val (c.2141C>T) pathogenic?

PGAP1 p.Ala714Val (c.2141C>T) is classified Uncertain significance in PGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-06). AlphaMissense: likely benign (0.0893); Ultra-rare (popmax 0.0103%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAP1 p.Ala714Val (c.2141C>T)?

PGAP1 p.Ala714Val (c.2141C>T) is associated with Inborn genetic diseases, intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Ala714Val (c.2141C>T) in the general population?

PGAP1 p.Ala714Val (c.2141C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about PGAP1 p.Ala714Val (c.2141C>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

PGAP1 p.Ala714Val

c.2141C>T · rs759027447 · VCV1910085

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	17.47	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 0.0103% European (non-Finnish) · 121/1,178,968 alleles

Filtering AF 0.00876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00821%

Overall 0.00769% 124/1,612,208 alleles · ultra-rare exomes 120/1,460,146 · genomes 4/152,062 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,744
Remaining individualsnot grpmax-eligible	0.00481%	20,801

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.Ala714Val
Coding: c.2141C>T
MANE Select: NM_024989
dbSNP: rs759027447
Type: single nucleotide variant
Location: chr2:196847012 (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

Disease context

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

Also linked: intellectual disability, autosomal recessive 42

Similar variants

PGAP1 p.Gln466Ter Pathogenic ★★ same condition
PGAP1 p.Gln555Ter Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Tyr758Ter Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala864Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg231Gln Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg250His Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg803Cys 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/pgap1-p-ala714val (accessed [today's date]).

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