Is PRPH p.Pro23= (c.69A>G) pathogenic?

PRPH p.Pro23= (c.69A>G) is classified Likely benign in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-18). Rare (popmax 0.191%, afr).

How common is PRPH p.Pro23= (c.69A>G) in the general population?

PRPH p.Pro23= (c.69A>G) is rare (popmax 0.191%, afr) (gnomAD).

PRPH p.Pro23=

c.69A>G · rs148091249 · VCV736884

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.191%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.2	GERP -2.8
Overall
CADD	4.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.191% African / African-American · 143/74,956 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.156%

Overall 0.0104% 167/1,611,728 alleles · rare exomes 95/1,459,558 · genomes 72/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.191%	524
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0208%	4,803
Admixed American	0.00334%	29,978
European (non-Finnish)	0.000424%	235,934

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.Pro23=
Coding: c.69A>G
MANE Select: NM_006262
dbSNP: rs148091249
Type: single nucleotide variant
Location: chr12:49295269 (GRCh38)

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

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-pro23 (accessed [today's date]).

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