Is ARHGAP19 p.Leu320Phe (c.960G>C) pathogenic?

ARHGAP19 p.Leu320Phe (c.960G>C) is classified Uncertain significance in ARHGAP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0951); Absent from gnomAD v4.1.

How common is ARHGAP19 p.Leu320Phe (c.960G>C) in the general population?

ARHGAP19 p.Leu320Phe (c.960G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP19 p.Leu320Phe (c.960G>C)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

ARHGAP19 p.Leu320Phe

c.960G>C · rs2493381223 · VCV2244428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.24	GERP -3.3, phastCons 0.093
Regional constraint	o/e 0.94	unconstrained · MANE · 67 kb · p 0.15 · regional, not allelic
Overall
CADD	16.81	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP19
Protein: p.Leu320Phe
Coding: c.960G>C
MANE Select: NM_032900
dbSNP: rs2493381223
Type: single nucleotide variant
Location: chr10:97246305 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.40

Full ARHGAP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP19 p.Ala329Ser Uncertain significance ★ ⚠ same type
ARHGAP19 p.Ala348Pro Uncertain significance ★ ⚠ same type
ARHGAP19 p.Ala418Thr Uncertain significance ★ ⚠ same type
ARHGAP19 p.Arg106Gln Uncertain significance ★ ⚠ same type
ARHGAP19 p.Arg223Trp Uncertain significance ★ ⚠ same type
ARHGAP19 p.Arg240His Uncertain significance ★ same type
ARHGAP19 p.Arg319Ile Uncertain significance ★ same type
ARHGAP19 p.Arg353Gln 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/arhgap19-p-leu320phe (accessed [today's date]).

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