Is PRPH p.Ala49Val (c.146C>T) pathogenic?

PRPH p.Ala49Val (c.146C>T) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: likely benign (0.0871); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRPH p.Ala49Val (c.146C>T)?

PRPH p.Ala49Val (c.146C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRPH p.Ala49Val (c.146C>T) in the general population?

PRPH p.Ala49Val (c.146C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPH p.Ala49Val (c.146C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

PRPH p.Ala49Val

c.146C>T · rs2498980229 · VCV2609206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.65, phastCons 0.84
Regional constraint	o/e 0.91	unconstrained · MANE · 3,149 bp · p 0.024 · regional, not allelic
Overall
CADD	16.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ala49Val
Coding: c.146C>T
MANE Select: NM_006262
dbSNP: rs2498980229
Type: single nucleotide variant
Location: chr12:49295346 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 49: 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.Ala67Pro 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-ala49val (accessed [today's date]).

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