Is RHO p.Phe91= (c.273C>T) pathogenic?

RHO p.Phe91= (c.273C>T) is classified Uncertain significance in RHO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.00446%, eas); Associated with inherited retinal dystrophy.

What condition is associated with RHO p.Phe91= (c.273C>T)?

RHO p.Phe91= (c.273C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is RHO p.Phe91= (c.273C>T) in the general population?

RHO p.Phe91= (c.273C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

RHO p.Phe91=

c.273C>T · rs2533020094 · VCV3027573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.2, phastCons 1
Overall
CADD	11.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,872 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,614,218 alleles · very rare exomes 3/1,461,892 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,436
European (non-Finnish)	8.47e-05%	1,180,054

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: RHO
Protein: p.Phe91=
Coding: c.273C>T
MANE Select: NM_000539
dbSNP: rs2533020094
Type: single nucleotide variant
Location: chr3:129529006 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 4 PDB
Residue 91: an α-helix

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RHO c.937-1G>T Pathogenic ★★ same condition
RHO c.937-2A>G Pathogenic/Likely pathogenic ★★ same condition
RHO c.937-2A>T Pathogenic/Likely pathogenic ★★ same condition
RHO p.Ala164Glu Pathogenic ★★ same condition
RHO p.Ala164Val Pathogenic/Likely pathogenic ★★ same condition
RHO p.Arg135Trp Pathogenic ★★ same condition
RHO p.Asn15Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
RHO p.Asp190Asn Pathogenic/Likely pathogenic ★★ same condition

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-phe91 (accessed [today's date]).

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