Is PRLR p.Pro447= (c.1341G>A) pathogenic?

PRLR p.Pro447= (c.1341G>A) is classified Likely benign in PRLR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). Ultra-rare (popmax 0.0133%, afr).

How common is PRLR p.Pro447= (c.1341G>A) in the general population?

PRLR p.Pro447= (c.1341G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

PRLR p.Pro447=

c.1341G>A · VCV4969849

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

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 -7.6	GERP -3.4
Overall
CADD	0.826	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,952 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.0013% 21/1,613,888 alleles · ultra-rare exomes 13/1,461,888 · genomes 8/152,000 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,495
East Asian	0.00446%	22,428
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,056
European (non-Finnish)	0.000424%	235,985

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: PRLR
Protein: p.Pro447=
Coding: c.1341G>A
MANE Select: NM_000949
Type: single nucleotide variant
Location: chr5:35065617 (GRCh38)
Gene constraint: LOEUF 0.438 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.67 · 12 PDB

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

Similar variants

PRLR p.Glu485Ala Uncertain significance ★★ ⚠ same type
PRLR p.Ile79Val Uncertain significance ★★ ⚠ same type
PRLR p.Thr490Met Uncertain significance ★★ ⚠ same type
PRLR c.685+7G>A Benign ★★ same type
PRLR p.Glu470= Benign ★★ same type
PRLR p.Leu284Trp Likely pathogenic ★ ⚠ same type
PRLR p.Ala185Ser Uncertain significance ★ ⚠ same type
PRLR p.Ala221Val 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/prlr-p-pro447 (accessed [today's date]).

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