Is AGAP1 p.Arg313His (c.938G>A) pathogenic?

AGAP1 p.Arg313His (c.938G>A) is classified Uncertain significance in AGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.9753); Very rare (popmax 0.00127%, nfe).

How common is AGAP1 p.Arg313His (c.938G>A) in the general population?

AGAP1 p.Arg313His (c.938G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about AGAP1 p.Arg313His (c.938G>A)?

AlphaMissense predicts likely pathogenic (score 0.9753) — an in-silico prediction, not a clinical call.

AGAP1 p.Arg313His

c.938G>A · rs1435028150 · VCV2081307

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9753	likely pathogenic
REVEL	0.405	indeterminate
SaProt	LLR -14.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00127% European (non-Finnish) · 15/1,180,024 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,614,122 alleles · very rare exomes 18/1,461,866 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)grpmax	0.00127%	78,668

Remaining individuals 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: AGAP1
Protein: p.Arg313His
Coding: c.938G>A
MANE Select: NM_001037131
dbSNP: rs1435028150
Type: single nucleotide variant
Location: chr2:235799503 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 313: the 'disordered' region

Full AGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg696Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg770Cys Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg798Gln Uncertain significance ★★ ⚠ same type

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/agap1-p-arg313his (accessed [today's date]).

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