Is PRPH2 p.Arg142Trp (c.424C>T) pathogenic?

PRPH2 p.Arg142Trp (c.424C>T) is classified Pathogenic/Likely pathogenic in PRPH2 (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-07-23). Very rare (popmax 0.005%, amr); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Arg142Trp (c.424C>T)?

PRPH2 p.Arg142Trp (c.424C>T) is associated with PRPH2-related disorder, cone dystrophy, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Arg142Trp (c.424C>T) in the general population?

PRPH2 p.Arg142Trp (c.424C>T) is very rare (popmax 0.005%, amr) (gnomAD).

PRPH2 p.Arg142Trp

c.424C>T · rs61755783 · VCV13183

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.635	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP -1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000805% 13/1,614,030 alleles · very rare exomes 11/1,461,894 · genomes 2/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000763%	131,115

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.Arg142Trp
Coding: c.424C>T
MANE Select: NM_000322
dbSNP: rs61755783
Type: single nucleotide variant
Location: chr6:42721911 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 142: a UniProt-annotated variant site (in rp7; also found in a patient with central areolar choroidal dystrophy)

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

Disease context

Also linked: cone dystrophy patterned macular dystrophy 1 choroidal dystrophy, central areolar 2 patterned dystrophy of the retinal pigment epithelium inherited retinal dystrophy retinitis pigmentosa Stargardt disease

Similar variants

PRPH2 p.Arg142Gln Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Arg142fs 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
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-arg142trp (accessed [today's date]).

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