Is ARHGAP45 p.Ala426Val (c.1277C>T) pathogenic?

ARHGAP45 p.Ala426Val (c.1277C>T) is classified Benign in ARHGAP45 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-11-15). AlphaMissense: likely benign (0.136); Low-frequency (popmax 4.06%, afr).

How common is ARHGAP45 p.Ala426Val (c.1277C>T) in the general population?

ARHGAP45 p.Ala426Val (c.1277C>T) is low-frequency (popmax 4.06%, afr) (gnomAD).

What do computational predictors say about ARHGAP45 p.Ala426Val (c.1277C>T)?

AlphaMissense predicts likely benign (score 0.136) — an in-silico prediction, not a clinical call.

ARHGAP45 p.Ala426Val

c.1277C>T · rs75236288 · VCV771775

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.136 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.06%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.136	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 12 kb · p 0.048 · regional, not allelic
Overall
CADD	22.0	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 4.06% African / African-American · 2,971/73,224 alleles

Filtering AF 3.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.89%

Overall 0.224% 3,474/1,553,736 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.06%	25
Admixed American	0.369%	271
Remaining individualsnot grpmax-eligible	0.316%	317
Middle Eastern	0.184%	545
South Asian	0.0095%	10,528
European (non-Finnish)	0.00906%	11,040
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,666

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.Ala426Val
Coding: c.1277C>T
MANE Select: NM_012292
dbSNP: rs75236288
Type: single nucleotide variant
Location: chr19:1077948 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.96 · 2 PDB
Residue 426: the f-bar 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.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
ARHGAP45 p.Val805= 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-ala426val (accessed [today's date]).

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