Is PRPH p.Phe80Val (c.238T>G) pathogenic?

PRPH p.Phe80Val (c.238T>G) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.6115); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRPH p.Phe80Val (c.238T>G)?

PRPH p.Phe80Val (c.238T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRPH p.Phe80Val (c.238T>G) in the general population?

PRPH p.Phe80Val (c.238T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPH p.Phe80Val (c.238T>G)?

AlphaMissense predicts likely pathogenic (score 0.6115) — an in-silico prediction, not a clinical call.

PRPH p.Phe80Val

c.238T>G · VCV3425811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6115	likely pathogenic
REVEL	0.717	pathogenic-leaning
SaProt	LLR -10.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.83, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,149 bp · p 0.024 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRPH
Protein: p.Phe80Val
Coding: c.238T>G
MANE Select: NM_006262
Type: single nucleotide variant
Location: chr12:49295438 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 80: the 'head' 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-phe80val (accessed [today's date]).

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