Is PRPH2 p.Pro313Ser (c.937C>T) pathogenic?

PRPH2 p.Pro313Ser (c.937C>T) is classified Uncertain significance in PRPH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-17). Ultra-rare (popmax 0.022%, sas); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Pro313Ser (c.937C>T)?

PRPH2 p.Pro313Ser (c.937C>T) is associated with PRPH2-related disorder, cone-rod dystrophy (ClinVar).

How common is PRPH2 p.Pro313Ser (c.937C>T) in the general population?

PRPH2 p.Pro313Ser (c.937C>T) is ultra-rare (popmax 0.022%, sas) (gnomAD).

PRPH2 p.Pro313Ser

c.937C>T · rs746742888 · VCV973723

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.038	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.85	GERP -0.67, phastCons 0.85
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% South Asian · 20/91,080 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00124% 20/1,613,842 alleles · ultra-rare exomes 20/1,461,562 · genomes 0/152,280 · 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: PRPH2
Protein: p.Pro313Ser
Coding: c.937C>T
MANE Select: NM_000322
dbSNP: rs746742888
Type: single nucleotide variant
Location: chr6:42698399 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 313: a UniProt-annotated variant site (in)

Full PRPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: cone-rod dystrophy

Similar variants

PRPH2 p.Pro313Gln Uncertain significance ★ same residue
PRPH2 p.Pro313Leu Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Pro313= Likely benign ★ same residue
PRPH2 p.Pro313fs Pathogenic ★ same residue
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+1G>A Pathogenic ★★ same condition
PRPH2 c.828+1G>T Pathogenic ★★ same condition
PRPH2 c.828+2T>C 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/prph2-p-pro313ser (accessed [today's date]).

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