Is RDH5 p.Pro211fs (c.632_633del) pathogenic?

RDH5 p.Pro211fs (c.632633del) is classified Pathogenic/Likely pathogenic in RDH5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-05). Very rare (popmax 0.00549%, sas); Associated with RDH5-related disorder.

What condition is associated with RDH5 p.Pro211fs (c.632_633del)?

RDH5 p.Pro211fs (c.632_633del) is associated with RDH5-related disorder, inherited retinal dystrophy (ClinVar).

How common is RDH5 p.Pro211fs (c.632_633del) in the general population?

RDH5 p.Pro211fs (c.632_633del) is very rare (popmax 0.00549%, sas) (gnomAD).

RDH5 p.Pro211fs

c.632_633del · rs763855790 · VCV1452620

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

RDH5-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.046	GERP -4.2
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,088 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000496% 8/1,614,032 alleles · very rare exomes 7/1,461,800 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,486
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: RDH5
Protein: p.Pro211fs
Coding: c.632_633del
MANE Select: NM_002905
dbSNP: rs763855790
Type: Deletion
Location: chr12:55723948 (GRCh38)

Full RDH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RDH5-related disorder

Also linked: inherited retinal dystrophy

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/rdh5-p-pro211fs (accessed [today's date]).

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