Is PRCD p.Leu39Phe (c.117G>C) pathogenic?

PRCD p.Leu39Phe (c.117G>C) is classified Uncertain significance in PRCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0748); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRCD p.Leu39Phe (c.117G>C)?

PRCD p.Leu39Phe (c.117G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PRCD p.Leu39Phe (c.117G>C) in the general population?

PRCD p.Leu39Phe (c.117G>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about PRCD p.Leu39Phe (c.117G>C)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

PRCD p.Leu39Phe

c.117G>C · VCV3424584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ 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	0.0748	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.013	GERP -2
Regional constraint	o/e 0.84	unconstrained · MANE · 2,429 bp · p 0.19 · regional, not allelic
Overall
CADD	0.955	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,870 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00062% 10/1,613,586 alleles · very rare exomes 7/1,461,302 · genomes 3/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
South Asian	0.00439%	22,766
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Leu39Phe
Coding: c.117G>C
MANE Select: NM_001077620
Type: single nucleotide variant
Location: chr17:76540547 (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-leu39phe (accessed [today's date]).

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