Is ARHGAP45 p.Ser764= (c.2292C>T) pathogenic?

ARHGAP45 p.Ser764= (c.2292C>T) is classified Likely benign in ARHGAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Rare (popmax 0.184%, mid).

How common is ARHGAP45 p.Ser764= (c.2292C>T) in the general population?

ARHGAP45 p.Ser764= (c.2292C>T) is rare (popmax 0.184%, mid) (gnomAD).

ARHGAP45 p.Ser764=

c.2292C>T · rs368248990 · VCV2648899

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.184%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.75	GERP -2.8
Overall
CADD	3.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.184% Middle Eastern · 11/5,988 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0797%

Overall 0.0436% 690/1,581,366 alleles · rare exomes 628/1,429,154 · genomes 62/152,212 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.25%	80
Middle Easterngrpmax	0.184%	544
Remaining individualsnot grpmax-eligible	0.113%	886
South Asian	0.0756%	1,323
Admixed American	0.0161%	6,208
European (non-Finnish)	0.0144%	6,930
African / African-American	0.00675%	14,820
East Asian	0.00233%	42,980

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: ARHGAP45
Protein: p.Ser764=
Coding: c.2292C>T
MANE Select: NM_012292
dbSNP: rs368248990
Type: single nucleotide variant
Location: chr19:1081651 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.96 · 2 PDB
Residue 764: the rho-gap domain

Full ARHGAP45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP45 c.422-1836C>T Benign ★★ same type
ARHGAP45 p.Ala426Val Benign ★★ ⚠ same type
ARHGAP45 p.Arg139His Benign ★★ same type
ARHGAP45 p.Glu1090Gly Benign ★★ same type
ARHGAP45 p.Gly1019Arg Likely benign ★★ same type
ARHGAP45 p.Leu138= Benign ★★ same type
ARHGAP45 p.Pro1011= Benign ★★ same type
ARHGAP45 p.Ser1032= Benign ★★ 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/arhgap45-p-ser764 (accessed [today's date]).

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