Is ARHGAP27 p.Ser186Phe (c.557C>T) pathogenic?

ARHGAP27 p.Ser186Phe (c.557C>T) is classified Uncertain significance in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.2976); Very rare (popmax 0.00138%, afr).

How common is ARHGAP27 p.Ser186Phe (c.557C>T) in the general population?

ARHGAP27 p.Ser186Phe (c.557C>T) is very rare (popmax 0.00138%, afr) (gnomAD).

What do computational predictors say about ARHGAP27 p.Ser186Phe (c.557C>T)?

AlphaMissense predicts likely benign (score 0.2976) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Ser186Phe

c.557C>T · rs1439013514 · VCV2240956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00138%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2976	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.97	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 11	GERP 1.4, phastCons 1
Overall
CADD	27.5	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 0.00138% African / African-American · 1/72,526 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000259% 4/1,545,652 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00138%	72,526
European (non-Finnish)	0.000262%	381,829

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: ARHGAP27
Protein: p.Ser186Phe
Coding: c.557C>T
MANE Select: NM_001282290
dbSNP: rs1439013514
Type: single nucleotide variant
Location: chr17:45429723 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB

Full ARHGAP27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP27 c.657+107G>T Uncertain significance ★ same type
ARHGAP27 c.657+130G>A Uncertain significance ★ same type
ARHGAP27 c.657+26G>A Uncertain significance ★ same type
ARHGAP27 c.657+31G>A Uncertain significance ★ same type
ARHGAP27 c.657+34T>A Uncertain significance ★ same type
ARHGAP27 c.657+38G>A Uncertain significance ★ same type
ARHGAP27 c.657+49C>T Uncertain significance ★ same type
ARHGAP27 c.657+53C>T 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/arhgap27-p-ser186phe (accessed [today's date]).

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