Is PGAP1 p.Ala63Thr (c.187G>A) pathogenic?

PGAP1 p.Ala63Thr (c.187G>A) is classified Likely benign in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). AlphaMissense: likely benign (0.0935); Rare (popmax 0.259%, eas); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Ala63Thr (c.187G>A)?

PGAP1 p.Ala63Thr (c.187G>A) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Ala63Thr (c.187G>A) in the general population?

PGAP1 p.Ala63Thr (c.187G>A) is rare (popmax 0.259%, eas) (gnomAD).

What do computational predictors say about PGAP1 p.Ala63Thr (c.187G>A)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

PGAP1 p.Ala63Thr

c.187G>A · rs201585822 · VCV703900

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.259%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 42

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -3.97	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 1.8	GERP -0.92, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	20.6	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 0.259% East Asian · 116/44,790 alleles

Filtering AF 0.221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.012% 194/1,611,656 alleles · rare exomes 147/1,459,466 · genomes 47/152,190 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.259%	386
Remaining individualsnot grpmax-eligible	0.0529%	1,891
African / African-American	0.0427%	2,342
Admixed American	0.00669%	14,940
South Asian	0.0011%	90,546
European (non-Finnish)	0.000679%	147,349

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.Ala63Thr
Coding: c.187G>A
MANE Select: NM_024989
dbSNP: rs201585822
Type: single nucleotide variant
Location: chr2:196920111 (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

intellectual disability, autosomal recessive 42 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PGAP1 p.Ala63= Likely benign ★ same residue
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.Ala714Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg231Gln Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg250His 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-ala63thr (accessed [today's date]).

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