Is PRPH2 p.Pro313Leu (c.938C>T) pathogenic?

PRPH2 p.Pro313Leu (c.938C>T) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0848%, nfe); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Pro313Leu (c.938C>T)?

PRPH2 p.Pro313Leu (c.938C>T) is associated with PRPH2-related disorder, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Pro313Leu (c.938C>T) in the general population?

PRPH2 p.Pro313Leu (c.938C>T) is ultra-rare (popmax 0.0848%, nfe) (gnomAD).

PRPH2 p.Pro313Leu

c.938C>T · rs61748434 · VCV98721

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0848%, nfe)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 0.32, phastCons 0.94
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	15.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0848% European (non-Finnish) · 1,001/1,179,786 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.0716% 1,156/1,613,818 alleles · ultra-rare exomes 1,085/1,461,576 · genomes 71/152,242 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0896%	1,116
European (non-Finnish)grpmax	0.0848%	1,179
South Asian	0.0714%	1,401
African / African-American	0.0293%	3,410
Admixed American	0.0183%	5,455
Middle Eastern	0.0165%	6,062

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro313Leu
Coding: c.938C>T
MANE Select: NM_000322
dbSNP: rs61748434
Type: single nucleotide variant
Location: chr6:42698398 (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: fundus albipunctatus patterned macular dystrophy 1 adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy patterned dystrophy of the retinal pigment epithelium inherited retinal dystrophy retinitis pigmentosa Stargardt disease

Similar variants

PRPH2 p.Pro313Ser Uncertain significance ★★ same residue
PRPH2 p.Pro313Gln Uncertain significance ★ same residue
PRPH2 p.Pro313= Likely benign ★ same residue
PRPH2 p.Pro313fs Pathogenic ★ same residue
PRPH2 c.581+1G>A Pathogenic ★★ same condition
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.582-2A>T Pathogenic ★★ same condition
PRPH2 c.828+1G>A 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-pro313leu (accessed [today's date]).

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