Is AGAP1 p.His754= (c.2262C>T) pathogenic?

AGAP1 p.His754= (c.2262C>T) is classified Benign/Likely benign in AGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Rare (popmax 0.575%, amr).

How common is AGAP1 p.His754= (c.2262C>T) in the general population?

AGAP1 p.His754= (c.2262C>T) is rare (popmax 0.575%, amr) (gnomAD).

AGAP1 p.His754=

c.2262C>T · rs138222964 · VCV2046519

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.575%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.323	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.7
Overall
CADD	3.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.575% Admixed American · 345/59,986 alleles

Filtering AF 0.525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.506%

Overall 0.277% 4,461/1,612,204 alleles · rare exomes 4,096/1,459,870 · genomes 365/152,334 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.575%	174
European (non-Finnish)	0.313%	319
Remaining individualsnot grpmax-eligible	0.229%	436
South Asian	0.223%	448
Middle Eastern	0.0918%	1,089
African / African-American	0.0693%	1,443
Ashkenazi Jewishnot grpmax-eligible	0.0406%	2,463
Finnishnot grpmax-eligible	0.00947%	10,557

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.His754=
Coding: c.2262C>T
MANE Select: NM_001037131
dbSNP: rs138222964
Type: single nucleotide variant
Location: chr2:236120339 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB

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

Similar variants

AGAP1 p.His754Tyr Uncertain significance ★ ⚠ same residue
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

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-his754 (accessed [today's date]).

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