Is PRPH p.Tyr287Cys (c.860A>G) pathogenic?

PRPH p.Tyr287Cys (c.860A>G) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-29). AlphaMissense: likely pathogenic (0.9775); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRPH p.Tyr287Cys (c.860A>G)?

PRPH p.Tyr287Cys (c.860A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRPH p.Tyr287Cys (c.860A>G) in the general population?

PRPH p.Tyr287Cys (c.860A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about PRPH p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

PRPH p.Tyr287Cys

c.860A>G · rs372095080 · VCV1050072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9775	likely pathogenic · top 10% in PRPH
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.30	donor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,149 bp · p 0.024 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,902 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,613,740 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,726
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000169%	589,977

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: PRPH
Protein: p.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_006262
dbSNP: rs372095080
Type: single nucleotide variant
Location: chr12:49297046 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 287: the if rod domain; the 'coil 2' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH p.Glu233Lys Uncertain significance ★★ ⚠ same condition
PRPH p.Ile419Met Uncertain significance ★★ ⚠ same condition
PRPH p.Ala109Val Uncertain significance ★ ⚠ same condition
PRPH p.Ala132Thr Uncertain significance ★ ⚠ same condition
PRPH p.Ala132Val Uncertain significance ★ ⚠ same condition
PRPH p.Ala193Glu Uncertain significance ★ ⚠ same condition
PRPH p.Ala193Gly Uncertain significance ★ ⚠ same condition
PRPH p.Ala49Val Uncertain significance ★ ⚠ 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/prph-p-tyr287cys (accessed [today's date]).

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