Is AGAP1 p.Pro514His (c.1541C>A) pathogenic?

AGAP1 p.Pro514His (c.1541C>A) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-27). AlphaMissense: ambiguous (0.3537); Ultra-rare (popmax 0.0167%, mid).

How common is AGAP1 p.Pro514His (c.1541C>A) in the general population?

AGAP1 p.Pro514His (c.1541C>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about AGAP1 p.Pro514His (c.1541C>A)?

AlphaMissense predicts ambiguous (score 0.3537) — an in-silico prediction, not a clinical call.

AGAP1 p.Pro514His

c.1541C>A · rs2469952768 · VCV2184077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3537 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Computational evidence

Protein change
AlphaMissense	0.3537	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -11.73	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	29.6	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 0.0167% Middle Eastern · 1/5,980 alleles

Overall 6.27e-05% 1/1,595,746 alleles · ultra-rare exomes 0/1,446,254 · genomes 1/149,492 · 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: AGAP1
Protein: p.Pro514His
Coding: c.1541C>A
MANE Select: NM_001037131
dbSNP: rs2469952768
Type: single nucleotide variant
Location: chr2:235968519 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 514: the 'disordered' region; the ph domain

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

Similar variants

AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala570Gly Uncertain significance ★★ same type
AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg696Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg770Cys 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-pro514his (accessed [today's date]).

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