Is PGAP1 p.Ile104Val (c.310A>G) pathogenic?

PGAP1 p.Ile104Val (c.310A>G) is classified Likely benign in PGAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-02). AlphaMissense: likely benign (0.0546); Ultra-rare (popmax 0.0274%, amr); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Ile104Val (c.310A>G)?

PGAP1 p.Ile104Val (c.310A>G) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Ile104Val (c.310A>G) in the general population?

PGAP1 p.Ile104Val (c.310A>G) is ultra-rare (popmax 0.0274%, amr) (gnomAD).

What do computational predictors say about PGAP1 p.Ile104Val (c.310A>G)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

PGAP1 p.Ile104Val

c.310A>G · rs200242648 · VCV771633

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 42

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.7	GERP -3.9
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	0.976	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 0.0274% Admixed American · 16/58,328 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0206% 331/1,606,152 alleles · ultra-rare exomes 304/1,453,966 · genomes 27/152,186 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.577%	173
Remaining individualsnot grpmax-eligible	0.0467%	2,143
Admixed Americangrpmax	0.0274%	3,645
European (non-Finnish)	0.00926%	10,799
South Asian	0.00448%	22,339
African / African-American	0.00403%	24,835
East Asian	0.00224%	44,692

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile104Val
Coding: c.310A>G
MANE Select: NM_024989
dbSNP: rs200242648
Type: single nucleotide variant
Location: chr2:196916585 (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-ile104val (accessed [today's date]).

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