Is PELP1 p.Pro55= (c.165G>T) pathogenic?

PELP1 p.Pro55= (c.165G>T) is classified Likely benign in PELP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Very rare (popmax 0.000339%, nfe).

How common is PELP1 p.Pro55= (c.165G>T) in the general population?

PELP1 p.Pro55= (c.165G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

PELP1 p.Pro55=

c.165G>T · VCV4566882

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 -4.2	GERP -3.3
Overall
CADD	0.967	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,740 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,606 alleles · very rare exomes 4/1,461,282 · genomes 0/152,324 · 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: PELP1
Protein: p.Pro55=
Coding: c.165G>T
MANE Select: NM_014389
Type: single nucleotide variant
Location: chr17:4703947 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 64.18 · 7 PDB
Residue 55: the 'required for modulation of esr1 transcriptional activity' region

Full PELP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PELP1 c.1157+1G>A Uncertain significance ★ same type
PELP1 c.1275-2A>G Uncertain significance ★ same type
PELP1 c.25C>G Uncertain significance ★ same type
PELP1 c.421-1G>T Uncertain significance ★ same type
PELP1 c.56G>T Uncertain significance ★ same type
PELP1 c.86C>G Uncertain significance ★ same type
PELP1 p.Ala14Val Uncertain significance ★ ⚠ same type
PELP1 p.Ala376Val 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/pelp1-p-pro55 (accessed [today's date]).

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