Is PRPH p.Glu128Val (c.383A>T) pathogenic?

PRPH p.Glu128Val (c.383A>T) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). AlphaMissense: ambiguous (0.4949); Ultra-rare (popmax 0.0271%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRPH p.Glu128Val (c.383A>T)?

PRPH p.Glu128Val (c.383A>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRPH p.Glu128Val (c.383A>T) in the general population?

PRPH p.Glu128Val (c.383A>T) is ultra-rare (popmax 0.0271%, sas) (gnomAD).

What do computational predictors say about PRPH p.Glu128Val (c.383A>T)?

AlphaMissense predicts ambiguous (score 0.4949) — an in-silico prediction, not a clinical call.

PRPH p.Glu128Val

c.383A>T · rs547795319 · VCV3219218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0271%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4949	ambiguous
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -11.38	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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 0.0271% South Asian · 23/84,874 alleles

Filtering AF 0.0185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00173% 27/1,558,328 alleles · ultra-rare exomes 25/1,406,056 · genomes 2/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0271%	3,690
Remaining individualsnot grpmax-eligible	0.00331%	30,193
European (non-Finnish)	0.000174%	575,805

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.Glu128Val
Coding: c.383A>T
MANE Select: NM_006262
dbSNP: rs547795319
Type: single nucleotide variant
Location: chr12:49295583 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 128: the if rod domain; the 'coil 1a' 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-glu128val (accessed [today's date]).

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