Is PRRC2A p.Pro2037Ser (c.6109C>T) pathogenic?

PRRC2A p.Pro2037Ser (c.6109C>T) is classified Uncertain significance in PRRC2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.0712); Ultra-rare (popmax 0.0825%, mid).

How common is PRRC2A p.Pro2037Ser (c.6109C>T) in the general population?

PRRC2A p.Pro2037Ser (c.6109C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about PRRC2A p.Pro2037Ser (c.6109C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

PRRC2A p.Pro2037Ser

c.6109C>T · rs141114290 · VCV2333687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -6.79	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 1.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,739 bp · p 0.034 · regional, not allelic
Overall
CADD	19.95	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

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.0141% 227/1,613,054 alleles · ultra-rare exomes 203/1,460,734 · genomes 24/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.06%	1,667
South Asian	0.0395%	2,530
Remaining individualsnot grpmax-eligible	0.0256%	3,906
European (non-Finnish)	0.0111%	9,008
African / African-American	0.004%	25,017

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.Pro2037Ser
Coding: c.6109C>T
MANE Select: NM_004638
dbSNP: rs141114290
Type: single nucleotide variant
Location: chr6:31636907 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 2037: the '3 x 50 aa type c repeats' 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-pro2037ser (accessed [today's date]).

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