Is RHO p.Val87Phe (c.259G>T) pathogenic?

RHO p.Val87Phe (c.259G>T) is classified Likely pathogenic in RHO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely pathogenic (0.8902); Absent from gnomAD v4.1.

How common is RHO p.Val87Phe (c.259G>T) in the general population?

RHO p.Val87Phe (c.259G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RHO p.Val87Phe (c.259G>T)?

AlphaMissense predicts likely pathogenic (score 0.8902) — an in-silico prediction, not a clinical call.

RHO p.Val87Phe

c.259G>T · rs2533020015 · VCV2578949

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8902 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8902	likely pathogenic ✓ concordant with ClinVar
REVEL	0.463	indeterminate
SaProt	LLR -10.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 4,981 bp · p 0.0028 · regional, not allelic
Overall
CADD	29.5	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

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: RHO
Protein: p.Val87Phe
Coding: c.259G>T
MANE Select: NM_000539
dbSNP: rs2533020015
Type: single nucleotide variant
Location: chr3:129528992 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 4 PDB
Residue 87: an α-helix; a UniProt-annotated variant site (in rp4)

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

Similar variants

RHO p.Val87Asp Likely pathogenic ★ ⚠ same residue
RHO c.696+1G>C Likely pathogenic ★★ same type
RHO c.936+1G>T Pathogenic/Likely pathogenic ★★ same type
RHO c.937-1G>A Pathogenic ★★ same type
RHO c.937-1G>T Pathogenic ★★ same type
RHO c.937-2A>G Pathogenic/Likely pathogenic ★★ same type
RHO c.937-2A>T Pathogenic/Likely pathogenic ★★ same type
RHO p.Ala164Glu Pathogenic ★★ 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/rho-p-val87phe (accessed [today's date]).

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