Is PRPH2 p.Ala342Ser (c.1024G>T) pathogenic?

PRPH2 p.Ala342Ser (c.1024G>T) is classified Uncertain significance in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.000509%, nfe); Associated with fundus albipunctatus.

What condition is associated with PRPH2 p.Ala342Ser (c.1024G>T)?

PRPH2 p.Ala342Ser (c.1024G>T) is associated with fundus albipunctatus, patterned macular dystrophy 1, adult-onset foveomacular vitelliform dystrophy (ClinVar).

How common is PRPH2 p.Ala342Ser (c.1024G>T) in the general population?

PRPH2 p.Ala342Ser (c.1024G>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

How is Fundus albipunctatus inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRPH2 p.Ala342Ser

c.1024G>T · rs1799983757 · VCV908891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

fundus albipunctatus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.089	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.59, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	15.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,836 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,806 alleles · very rare exomes 6/1,461,540 · genomes 0/152,266 · 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.Ala342Ser
Coding: c.1024G>T
MANE Select: NM_000322
dbSNP: rs1799983757
Type: single nucleotide variant
Location: chr6:42698312 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 342: the 'interaction with mreg' region

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

Disease context

fundus albipunctatus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: patterned macular dystrophy 1 adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy retinitis pigmentosa

For Fundus albipunctatus (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

PRPH2 p.Ala342Thr Uncertain significance ★ same residue
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
PRPH2 p.Arg172Trp Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg195Gln Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg195Leu 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-ala342ser (accessed [today's date]).

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