Is PRRC2A p.Pro1448= (c.4344G>A) pathogenic?

PRRC2A p.Pro1448= (c.4344G>A) is classified Likely benign in PRRC2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-01). Rare (popmax 0.103%, nfe); Associated with PRRC2A-related disorder.

What condition is associated with PRRC2A p.Pro1448= (c.4344G>A)?

PRRC2A p.Pro1448= (c.4344G>A) is associated with PRRC2A-related disorder (ClinVar).

How common is PRRC2A p.Pro1448= (c.4344G>A) in the general population?

PRRC2A p.Pro1448= (c.4344G>A) is rare (popmax 0.103%, nfe) (gnomAD).

PRRC2A p.Pro1448=

c.4344G>A · rs200399206 · VCV3052409

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.103%, 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 -6.6	GERP -3.8
Overall
CADD	1.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% European (non-Finnish) · 1,220/1,179,920 alleles

Filtering AF 0.0985% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0966%

Overall 0.0835% 1,347/1,612,878 alleles · rare exomes 1,248/1,460,598 · genomes 99/152,280 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.111%	899
European (non-Finnish)grpmax	0.103%	967
Remaining individualsnot grpmax-eligible	0.0656%	1,524
African / African-American	0.0187%	5,359
Admixed American	0.00167%	60,008
South Asian	0.0011%	91,080

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1448=
Coding: c.4344G>A
MANE Select: NM_004638
dbSNP: rs200399206
Type: single nucleotide variant
Location: chr6:31633403 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 40.07
Residue 1448: 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.Pro1448Leu 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-pro1448 (accessed [today's date]).

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