Is PRPH2 p.Lys15Arg (c.44A>G) pathogenic?

PRPH2 p.Lys15Arg (c.44A>G) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-12-02). Rare (popmax 0.123%, eas); Associated with patterned macular dystrophy 1.

What condition is associated with PRPH2 p.Lys15Arg (c.44A>G)?

PRPH2 p.Lys15Arg (c.44A>G) is associated with patterned macular dystrophy 1, fundus albipunctatus, adult-onset foveomacular vitelliform dystrophy (ClinVar).

How common is PRPH2 p.Lys15Arg (c.44A>G) in the general population?

PRPH2 p.Lys15Arg (c.44A>G) is rare (popmax 0.123%, eas) (gnomAD).

PRPH2 p.Lys15Arg

c.44A>G · rs555112175 · VCV910955

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, eas)

Conditions

patterned macular dystrophy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.239	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% East Asian · 55/44,892 alleles

Filtering AF 0.0966% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0873%

Overall 0.00341% 55/1,614,120 alleles · rare exomes 52/1,461,774 · genomes 3/152,346 · 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.Lys15Arg
Coding: c.44A>G
MANE Select: NM_000322
dbSNP: rs555112175
Type: single nucleotide variant
Location: chr6:42722291 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB

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

Disease context

patterned macular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fundus albipunctatus adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy inherited retinal dystrophy retinitis pigmentosa

Similar variants

PRPH2 p.Lys15Asn Uncertain significance ★ 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+3A>T Pathogenic ★★ same condition
PRPH2 c.829-4C>G Pathogenic ★★ same condition
PRPH2 p.Arg142Trp Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg172Gln 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-lys15arg (accessed [today's date]).

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