Is PRPH p.Arg164Trp (c.490C>T) pathogenic?

PRPH p.Arg164Trp (c.490C>T) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.325); Ultra-rare (popmax 0.0434%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRPH p.Arg164Trp (c.490C>T)?

PRPH p.Arg164Trp (c.490C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRPH p.Arg164Trp (c.490C>T) in the general population?

PRPH p.Arg164Trp (c.490C>T) is ultra-rare (popmax 0.0434%, sas) (gnomAD).

What do computational predictors say about PRPH p.Arg164Trp (c.490C>T)?

AlphaMissense predicts likely benign (score 0.325) — an in-silico prediction, not a clinical call.

PRPH p.Arg164Trp

c.490C>T · VCV3425807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.325 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0434%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.325	likely benign
REVEL	0.743	pathogenic-leaning
SaProt	LLR -12.65	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	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 0.0434% South Asian · 36/83,026 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0283%

Overall 0.00254% 39/1,532,734 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0434%	2,306
Remaining individualsnot grpmax-eligible	0.00168%	59,566
European (non-Finnish)	0.000175%	571,916

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.Arg164Trp
Coding: c.490C>T
MANE Select: NM_006262
Type: single nucleotide variant
Location: chr12:49295690 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 164: the if rod domain; the 'coil 1b' 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-arg164trp (accessed [today's date]).

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