Is AGAP1 p.Arg710Trp (c.2128C>T) pathogenic?

AGAP1 p.Arg710Trp (c.2128C>T) is classified Likely benign in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.1675); Rare (popmax 0.196%, afr).

How common is AGAP1 p.Arg710Trp (c.2128C>T) in the general population?

AGAP1 p.Arg710Trp (c.2128C>T) is rare (popmax 0.196%, afr) (gnomAD).

What do computational predictors say about AGAP1 p.Arg710Trp (c.2128C>T)?

AlphaMissense predicts likely benign (score 0.1675) — an in-silico prediction, not a clinical call.

AGAP1 p.Arg710Trp

c.2128C>T · rs143617959 · VCV2057328

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1675 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.196%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1675	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -15.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.79	GERP -0.51, phastCons 0.22
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	23.6	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 0.196% African / African-American · 147/75,014 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.0118% 190/1,611,374 alleles · rare exomes 98/1,459,024 · genomes 92/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.196%	510
Middle Eastern	0.0165%	6,050
Remaining individualsnot grpmax-eligible	0.0144%	6,930
Admixed American	0.0134%	7,485
South Asian	0.00441%	22,664
Finnishnot grpmax-eligible	0.00313%	31,922
European (non-Finnish)	0.00161%	62,022

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.Arg710Trp
Coding: c.2128C>T
MANE Select: NM_001037131
dbSNP: rs143617959
Type: single nucleotide variant
Location: chr2:236120205 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 710: the arf-gap domain

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

Similar variants

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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-arg710trp (accessed [today's date]).

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