Is PRRC2A p.Ala286= (c.858G>C) pathogenic?

PRRC2A p.Ala286= (c.858G>C) is classified Likely benign in PRRC2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Rare (popmax 0.16%, nfe); Associated with PRRC2A-related disorder.

What condition is associated with PRRC2A p.Ala286= (c.858G>C)?

PRRC2A p.Ala286= (c.858G>C) is associated with PRRC2A-related disorder (ClinVar).

How common is PRRC2A p.Ala286= (c.858G>C) in the general population?

PRRC2A p.Ala286= (c.858G>C) is rare (popmax 0.16%, nfe) (gnomAD).

PRRC2A p.Ala286=

c.858G>C · rs147717718 · VCV3053072

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.16%, nfe)

Conditions

PRRC2A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.1
Overall
CADD	0.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% European (non-Finnish) · 1,884/1,176,708 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.152%

Overall 0.127% 2,034/1,605,592 alleles · rare exomes 1,937/1,453,380 · genomes 97/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.16%	625
Remaining individualsnot grpmax-eligible	0.148%	676
Finnishnot grpmax-eligible	0.048%	2,082
African / African-American	0.0294%	3,404
Admixed American	0.00845%	11,839
East Asian	0.00223%	44,886

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: PRRC2A
Protein: p.Ala286=
Coding: c.858G>C
MANE Select: NM_004638
dbSNP: rs147717718
Type: single nucleotide variant
Location: chr6:31626038 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 286: 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

Disease context

PRRC2A-related disorder

Similar variants

PRRC2A p.Ala286Val Uncertain significance ★ ⚠ same residue
PRRC2A p.Lys308Arg Uncertain significance ⚠ same condition
PRRC2A c.391-6C>A Likely benign same condition
PRRC2A c.4720-6C>G Likely benign same condition
PRRC2A c.5624+9C>T Benign same condition
PRRC2A c.760-10C>G Likely benign same condition
PRRC2A c.*9C>T Likely benign same condition
PRRC2A p.Ala1222= Likely benign same condition

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-ala286 (accessed [today's date]).

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