Is PRRC2A p.Pro413His (c.1238C>A) pathogenic?

PRRC2A p.Pro413His (c.1238C>A) is classified Uncertain significance in PRRC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.2187); Absent from gnomAD v4.1.

How common is PRRC2A p.Pro413His (c.1238C>A) in the general population?

PRRC2A p.Pro413His (c.1238C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRRC2A p.Pro413His (c.1238C>A)?

AlphaMissense predicts likely benign (score 0.2187) — an in-silico prediction, not a clinical call.

PRRC2A p.Pro413His

c.1238C>A · VCV4145445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2187 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2187	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 7,920 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	23.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRRC2A
Protein: p.Pro413His
Coding: c.1238C>A
MANE Select: NM_004638
Type: single nucleotide variant
Location: chr6:31627146 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 413: the '4 x 57 aa type a repeats' region; the 'disordered' region; the '2 x type b repeats' region

Full PRRC2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRRC2A p.Pro413Ala Uncertain significance ★ ⚠ same residue
PRRC2A p.Ala1006Val Uncertain significance ★ ⚠ same type
PRRC2A p.Ala1268Thr Uncertain significance ★ ⚠ same type
PRRC2A p.Ala1302Pro Uncertain significance ★ ⚠ same type
PRRC2A p.Ala1361Gly Uncertain significance ★ ⚠ same type
PRRC2A p.Ala1405Pro Uncertain significance ★ ⚠ same type
PRRC2A p.Ala1405Val Uncertain significance ★ ⚠ same type
PRRC2A p.Ala145Thr 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/prrc2a-p-pro413his (accessed [today's date]).

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