Is PRCD p.Pro25Leu (c.74C>T) pathogenic?

PRCD p.Pro25Leu (c.74C>T) is classified Conflicting classifications of pathogenicity in PRCD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-30). AlphaMissense: ambiguous (0.4834); Ultra-rare (popmax 0.0379%, mid); Associated with PRCD-related disorders.

What condition is associated with PRCD p.Pro25Leu (c.74C>T)?

PRCD p.Pro25Leu (c.74C>T) is associated with PRCD-related disorders (ClinVar).

How common is PRCD p.Pro25Leu (c.74C>T) in the general population?

PRCD p.Pro25Leu (c.74C>T) is ultra-rare (popmax 0.0379%, mid) (gnomAD).

What do computational predictors say about PRCD p.Pro25Leu (c.74C>T)?

AlphaMissense predicts ambiguous (score 0.4834) — an in-silico prediction, not a clinical call.

PRCD p.Pro25Leu

c.74C>T · rs757471313 · VCV944910

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, mid)

Conditions

PRCD-related disorders

⚠ 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
AlphaMissense	0.4834	ambiguous
REVEL	0.643	indeterminate
SaProt	LLR -6.84	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,429 bp · p 0.19 · regional, not allelic
Overall
CADD	33.0	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 0.0379% Middle Eastern · 2/5,272 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00272%

Overall 0.00103% 15/1,454,554 alleles · ultra-rare exomes 13/1,332,072 · genomes 2/122,482 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0379%	2,636
East Asian	0.00563%	17,769
Finnishnot grpmax-eligible	0.00215%	46,540
African / African-American	0.0016%	62,614
European (non-Finnish)	0.000825%	121,160

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: PRCD
Protein: p.Pro25Leu
Coding: c.74C>T
MANE Select: NM_001077620
dbSNP: rs757471313
Type: single nucleotide variant
Location: chr17:76540215 (GRCh38)

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

Disease context

PRCD-related disorders

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/prcd-p-pro25leu (accessed [today's date]).

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