Is ARHGAP45 p.Pro110Leu (c.329C>T) pathogenic?

ARHGAP45 p.Pro110Leu (c.329C>T) is classified Uncertain significance in ARHGAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-09). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0164%, mid).

How common is ARHGAP45 p.Pro110Leu (c.329C>T) in the general population?

ARHGAP45 p.Pro110Leu (c.329C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ARHGAP45 p.Pro110Leu (c.329C>T)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

ARHGAP45 p.Pro110Leu

c.329C>T · rs751570740 · VCV2248801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -1.1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,268 bp · p 0.063 · regional, not allelic
Overall
CADD	12.41	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00105% 17/1,612,486 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00769%	13,011
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000678%	147,498

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.Pro110Leu
Coding: c.329C>T
MANE Select: NM_012292
dbSNP: rs751570740
Type: single nucleotide variant
Location: chr19:1068652 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.96 · 2 PDB
Residue 110: the 'disordered' region

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-pro110leu (accessed [today's date]).

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