Is PRCD p.Phe19Ile (c.55T>A) pathogenic?

PRCD p.Phe19Ile (c.55T>A) is classified Uncertain significance in PRCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-29). AlphaMissense: ambiguous (0.4792); Ultra-rare (popmax 0.027%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRCD p.Phe19Ile (c.55T>A)?

PRCD p.Phe19Ile (c.55T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRCD p.Phe19Ile (c.55T>A) in the general population?

PRCD p.Phe19Ile (c.55T>A) is ultra-rare (popmax 0.027%, nfe) (gnomAD).

What do computational predictors say about PRCD p.Phe19Ile (c.55T>A)?

AlphaMissense predicts ambiguous (score 0.4792) — an in-silico prediction, not a clinical call.

PRCD p.Phe19Ile

c.55T>A · rs199693977 · VCV1047492

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4792	ambiguous
REVEL	0.28	benign-leaning
SaProt	LLR -3.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.1	GERP 0.57, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,429 bp · p 0.19 · regional, not allelic
Overall
CADD	24.2	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 0.027% European (non-Finnish) · 312/1,157,310 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.02% 315/1,573,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.027%	3,709
Remaining individualsnot grpmax-eligible	0.00498%	20,084

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.Phe19Ile
Coding: c.55T>A
MANE Select: NM_134268 · reported on NM_001077620
dbSNP: rs199693977
Type: single nucleotide variant
Location: chr17:76540196 (GRCh38)

Full PRCD 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

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-phe19ile (accessed [today's date]).

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