Is PRCD p.Ala12Thr (c.34G>A) pathogenic?

PRCD p.Ala12Thr (c.34G>A) is classified Uncertain significance in PRCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-27). AlphaMissense: likely benign (0.3361); Ultra-rare (popmax 0.0249%, eas).

How common is PRCD p.Ala12Thr (c.34G>A) in the general population?

PRCD p.Ala12Thr (c.34G>A) is ultra-rare (popmax 0.0249%, eas) (gnomAD).

What do computational predictors say about PRCD p.Ala12Thr (c.34G>A)?

AlphaMissense predicts likely benign (score 0.3361) — an in-silico prediction, not a clinical call.

PRCD p.Ala12Thr

c.34G>A · rs779911519 · VCV1432905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0249%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.3361	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,429 bp · p 0.19 · regional, not allelic
Overall
CADD	27.6	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 0.0249% East Asian · 11/44,190 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.000939% 15/1,597,190 alleles · ultra-rare exomes 9/1,450,748 · genomes 6/146,442 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0249%	4,017
African / African-American	0.00411%	24,347
Remaining individualsnot grpmax-eligible	0.00162%	61,760

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.Ala12Thr
Coding: c.34G>A
MANE Select: NM_001077620
dbSNP: rs779911519
Type: single nucleotide variant
Location: chr17:76540175 (GRCh38)

Full PRCD 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/prcd-p-ala12thr (accessed [today's date]).

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