Is RHO p.Pro71Ser (c.211C>T) pathogenic?

RHO p.Pro71Ser (c.211C>T) is classified Uncertain significance in RHO (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-01). AlphaMissense: likely pathogenic (0.8052); Very rare (popmax 0.0011%, sas); Associated with retinitis pigmentosa 4.

What condition is associated with RHO p.Pro71Ser (c.211C>T)?

RHO p.Pro71Ser (c.211C>T) is associated with retinitis pigmentosa 4 (ClinVar).

How common is RHO p.Pro71Ser (c.211C>T) in the general population?

RHO p.Pro71Ser (c.211C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RHO p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.8052) — an in-silico prediction, not a clinical call.

RHO p.Pro71Ser

c.211C>T · rs1305158106 · VCV984777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 4

Computational evidence

Protein change
AlphaMissense	0.8052	likely pathogenic
REVEL	0.668	pathogenic-leaning
SaProt	LLR -11.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 4,981 bp · p 0.0028 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,088 alleles

Overall 6.19e-05% 1/1,614,244 alleles · very rare exomes 1/1,461,890 · genomes 0/152,354 · joint denominator

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.Pro71Ser
Coding: c.211C>T
MANE Select: NM_000539
dbSNP: rs1305158106
Type: single nucleotide variant
Location: chr3:129528944 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 4 PDB
Residue 71: a turn; a UniProt-annotated variant site (in rp4)

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

Disease context

retinitis pigmentosa 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RHO c.936+1G>T Pathogenic/Likely 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.Arg135Leu Pathogenic ★★ same condition
RHO p.Arg135Trp Pathogenic ★★ same condition
RHO p.Asn15Ser 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-pro71ser (accessed [today's date]).

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