Is PRRC2A p.Ser1386Pro (c.4156T>C) pathogenic?

PRRC2A p.Ser1386Pro (c.4156T>C) is classified Uncertain significance in PRRC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.9547); Absent from gnomAD v4.1.

How common is PRRC2A p.Ser1386Pro (c.4156T>C) in the general population?

PRRC2A p.Ser1386Pro (c.4156T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRRC2A p.Ser1386Pro (c.4156T>C)?

AlphaMissense predicts likely pathogenic (score 0.9547) — an in-silico prediction, not a clinical call.

PRRC2A p.Ser1386Pro

c.4156T>C · VCV4572651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9547 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9547	likely pathogenic · top 9% in PRRC2A
REVEL	0.393	indeterminate
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 7,920 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	24.1	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

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.Ser1386Pro
Coding: c.4156T>C
MANE Select: NM_004638
Type: single nucleotide variant
Location: chr6:31632829 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 1386: a modified residue (phosphoserine); the '4 x 57 aa type a repeats' region; the 'disordered' region

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

Similar variants

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
PRRC2A p.Ala1474Thr 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-ser1386pro (accessed [today's date]).

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