Is PRRC2A p.Pro2006Ser (c.6016C>T) pathogenic?

PRRC2A p.Pro2006Ser (c.6016C>T) is classified Benign in PRRC2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). AlphaMissense: likely benign (0.1645); Common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with PRRC2A-related disorder.

What condition is associated with PRRC2A p.Pro2006Ser (c.6016C>T)?

PRRC2A p.Pro2006Ser (c.6016C>T) is associated with PRRC2A-related disorder (ClinVar).

What do computational predictors say about PRRC2A p.Pro2006Ser (c.6016C>T)?

AlphaMissense predicts likely benign (score 0.1645) — an in-silico prediction, not a clinical call.

PRRC2A p.Pro2006Ser

Q: How common is PRRC2A p.Pro2006Ser (c.6016C>T) in the general population?

PRRC2A p.Pro2006Ser (c.6016C>T) is common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6016C>T · rs10885 · VCV3058971

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1645 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 19.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PRRC2A-related disorder

Computational evidence

Protein change
AlphaMissense	0.1645	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -7.16	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	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,739 bp · p 0.034 · regional, not allelic
Overall
CADD	22.2	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 19.9% African / African-American · 14,903/74,988 alleles

Filtering AF 19.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.5%

Overall 17.5% 282,605/1,610,838 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.9%	5
European (non-Finnish)	19.1%	5
Amishnot grpmax-eligible	17.4%	6
Remaining individualsnot grpmax-eligible	16.5%	6
Finnishnot grpmax-eligible	16.1%	6
Ashkenazi Jewishnot grpmax-eligible	11.9%	8
South Asian	11.5%	9
Middle Eastern	9.53%	10
Admixed American	8.49%	12
East Asian	5.04%	20

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.Pro2006Ser
Coding: c.6016C>T
MANE Select: NM_004638
dbSNP: rs10885
Type: single nucleotide variant
Location: chr6:31636814 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 2006: a UniProt-annotated variant site (in); the '3 x 50 aa type c repeats' region

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

Disease context

PRRC2A-related disorder

Similar variants

PRRC2A p.Pro2006Leu 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-pro2006ser (accessed [today's date]).

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