Is CYP2W1 p.Arg231Trp (c.691C>T) pathogenic?

CYP2W1 p.Arg231Trp (c.691C>T) is classified Uncertain significance in CYP2W1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). AlphaMissense: likely benign (0.1721); Ultra-rare (popmax 0.0134%, eas).

How common is CYP2W1 p.Arg231Trp (c.691C>T) in the general population?

CYP2W1 p.Arg231Trp (c.691C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CYP2W1 p.Arg231Trp (c.691C>T)?

AlphaMissense predicts likely benign (score 0.1721) — an in-silico prediction, not a clinical call.

CYP2W1 p.Arg231Trp

c.691C>T · rs1031091197 · VCV2223821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1721	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.43	GERP -1.8, phastCons 0.059
Regional constraint	o/e 1.07	unconstrained · MANE · 5,607 bp · p 0.082 · regional, not allelic
Overall
CADD	23.0	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 0.0134% East Asian · 6/44,890 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00205% 33/1,612,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
Remaining individualsnot grpmax-eligible	0.0032%	31,228
African / African-American	0.00267%	37,467
European (non-Finnish)	0.00195%	51,300

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: CYP2W1
Protein: p.Arg231Trp
Coding: c.691C>T
MANE Select: NM_001318252 · reported on NM_017781
dbSNP: rs1031091197
Type: single nucleotide variant
Location: chr7:986669 (GRCh38)

Full CYP2W1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/cyp2w1-p-arg231trp (accessed [today's date]).

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