Is PRRC2C p.Ser895Phe (c.2684C>T) pathogenic?

PRRC2C p.Ser895Phe (c.2684C>T) is classified Uncertain significance in PRRC2C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). Very rare (popmax 0.000254%, nfe).

How common is PRRC2C p.Ser895Phe (c.2684C>T) in the general population?

PRRC2C p.Ser895Phe (c.2684C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

PRRC2C p.Ser895Phe

c.2684C>T · rs772889986 · VCV2488867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.1, phastCons 0.76
Regional constraint	o/e 0.95	unconstrained · MANE · 18 kb · p 0.043 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,858 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,894 alleles · very rare exomes 3/1,461,656 · genomes 0/152,238 · joint denominator

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: PRRC2C
Protein: p.Ser895Phe
Coding: c.2684C>T
MANE Select: NM_001387844
dbSNP: rs772889986
Type: single nucleotide variant
Location: chr1:171540150 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Residue 895: the 'disordered' region

Full PRRC2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRRC2C c.1055+2T>C Uncertain significance ★ same type
PRRC2C p.Ala104Thr Uncertain significance ★ same type
PRRC2C p.Ala1120Thr Uncertain significance ★ same type
PRRC2C p.Ala1762Ser Uncertain significance ★ same type
PRRC2C p.Ala1774Ser Uncertain significance ★ same type
PRRC2C p.Ala1785Val Uncertain significance ★ same type
PRRC2C p.Ala1927Thr Uncertain significance ★ same type
PRRC2C p.Ala1930Val 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/prrc2c-p-ser895phe (accessed [today's date]).

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