Is PGAP1 p.Lys317= (c.951A>G) pathogenic?

PGAP1 p.Lys317= (c.951A>G) is classified Likely benign in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Ultra-rare (popmax 0.0135%, eas); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Lys317= (c.951A>G)?

PGAP1 p.Lys317= (c.951A>G) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Lys317= (c.951A>G) in the general population?

PGAP1 p.Lys317= (c.951A>G) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

PGAP1 p.Lys317=

c.951A>G · rs760960656 · VCV2739590

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

Conditions

intellectual disability, autosomal recessive 42

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP 0.33, phastCons 1
Overall
CADD	8.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% East Asian · 6/44,412 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.000376% 6/1,594,002 alleles · ultra-rare exomes 5/1,441,818 · genomes 1/152,184 · 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: PGAP1
Protein: p.Lys317=
Coding: c.951A>G
MANE Select: NM_024989
dbSNP: rs760960656
Type: single nucleotide variant
Location: chr2:196893222 (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.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
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-lys317 (accessed [today's date]).

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