Is PRCC p.Glu322Asp (c.966A>T) pathogenic?

PRCC p.Glu322Asp (c.966A>T) is classified Uncertain significance in PRCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: ambiguous (0.4204); Very rare (popmax 0.00271%, nfe).

How common is PRCC p.Glu322Asp (c.966A>T) in the general population?

PRCC p.Glu322Asp (c.966A>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about PRCC p.Glu322Asp (c.966A>T)?

AlphaMissense predicts ambiguous (score 0.4204) — an in-silico prediction, not a clinical call.

PRCC p.Glu322Asp

c.966A>T · VCV3937647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4204	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -5.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP -4.3, phastCons 0.01
Regional constraint	o/e 1.08	unconstrained · MANE · 4,824 bp · p 0.34 · regional, not allelic
Overall
CADD	9.71	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 0.00271% European (non-Finnish) · 32/1,180,014 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00204% 33/1,614,054 alleles · very rare exomes 29/1,461,874 · genomes 4/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,875
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: PRCC
Protein: p.Glu322Asp
Coding: c.966A>T
MANE Select: NM_005973
Type: single nucleotide variant
Location: chr1:156787057 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.89

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

Similar variants

PRCC p.Asp341Gly Uncertain significance ★★ ⚠ same type
PRCC p.Ala283Thr Uncertain significance ★ ⚠ same type
PRCC p.Ala356Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg219Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg467Gln Uncertain significance ★ ⚠ same type
PRCC p.Arg482Cys Uncertain significance ★ ⚠ same type
PRCC p.Asn189Ser Uncertain significance ★ ⚠ same type
PRCC p.Asp214His Uncertain significance ★ ⚠ same type

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/prcc-p-glu322asp (accessed [today's date]).

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