Is CWH43 p.Val289Phe (c.865G>T) pathogenic?

CWH43 p.Val289Phe (c.865G>T) is classified Uncertain significance in CWH43 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely benign (0.1043); Very rare (popmax 8.47e-05%, nfe).

How common is CWH43 p.Val289Phe (c.865G>T) in the general population?

CWH43 p.Val289Phe (c.865G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CWH43 p.Val289Phe (c.865G>T)?

AlphaMissense predicts likely benign (score 0.1043) — an in-silico prediction, not a clinical call.

CWH43 p.Val289Phe

c.865G>T · rs1783069130 · VCV2404842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1043	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.83	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 2.2	GERP 0.57, phastCons 0.59
Regional constraint	o/e 1.12	unconstrained · MANE · 58 kb · p 0.0048 · regional, not allelic
Overall
CADD	15.74	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 8.47e-05% European (non-Finnish) · 1/1,179,942 alleles

Overall 6.84e-05% 1/1,461,708 alleles · very rare

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: CWH43
Protein: p.Val289Phe
Coding: c.865G>T
MANE Select: NM_025087
dbSNP: rs1783069130
Type: single nucleotide variant
Location: chr4:49003797 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.45

Full CWH43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CWH43 p.Ala626Val Benign ★★ ⚠ same type
CWH43 p.Glu516Gln Benign ★★ same type
CWH43 p.Ile78Val Benign ★★ same type
CWH43 p.Ala190Thr Uncertain significance ★ ⚠ same type
CWH43 p.Ala246Val Uncertain significance ★ ⚠ same type
CWH43 p.Ala272Val Uncertain significance ★ ⚠ same type
CWH43 p.Ala273Val Uncertain significance ★ ⚠ same type
CWH43 p.Ala291Thr 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/cwh43-p-val289phe (accessed [today's date]).

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