Is PRPH2 p.Ser198= (c.594C>T) pathogenic?

PRPH2 p.Ser198= (c.594C>T) is classified Likely benign in PRPH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-13). Ultra-rare (popmax 0.0721%, afr); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Ser198= (c.594C>T)?

PRPH2 p.Ser198= (c.594C>T) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Ser198= (c.594C>T) in the general population?

PRPH2 p.Ser198= (c.594C>T) is ultra-rare (popmax 0.0721%, afr) (gnomAD).

PRPH2 p.Ser198=

c.594C>T · rs375978676 · VCV1149457

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0721%, afr)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.5	GERP 0.59, phastCons 1
Overall
CADD	13.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0721% African / African-American · 54/74,916 alleles

Filtering AF 0.0567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0512%

Overall 0.00372% 60/1,614,068 alleles · ultra-rare exomes 29/1,461,890 · genomes 31/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0721%	1,387
Admixed American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: PRPH2
Protein: p.Ser198=
Coding: c.594C>T
MANE Select: NM_000322
dbSNP: rs375978676
Type: single nucleotide variant
Location: chr6:42704599 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 198: a UniProt-annotated variant site (in rp7; decreased protein expression)

Full PRPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PRPH2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH2 p.Ser198Thr Uncertain significance ★ same residue
PRPH2 p.Ser198Arg Pathogenic same residue
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+1G>A Pathogenic ★★ same condition
PRPH2 c.828+1G>T Pathogenic ★★ same condition
PRPH2 c.828+2T>C Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+3A>T Pathogenic ★★ same condition
PRPH2 p.Arg142Trp Pathogenic/Likely pathogenic ★★ 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/prph2-p-ser198 (accessed [today's date]).

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