Is ESR1 p.Pro152= (c.456A>G) pathogenic?

ESR1 p.Pro152= (c.456A>G) is classified Likely benign in ESR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-16). Very rare (popmax 0.00267%, afr).

How common is ESR1 p.Pro152= (c.456A>G) in the general population?

ESR1 p.Pro152= (c.456A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

ESR1 p.Pro152=

c.456A>G · rs758203894 · VCV724348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.356	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -0.7, phastCons 0.003
Overall
CADD	3.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,216 alleles · very rare exomes 1/1,461,036 · genomes 1/152,180 · 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: ESR1
Protein: p.Pro152=
Coding: c.456A>G
MANE Select: NM_000125
dbSNP: rs758203894
Type: single nucleotide variant
Location: chr6:151842600 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 492 PDB
Residue 152: the 'modulating (transactivation af-1); mediates interaction with macrod1' region; the 'interaction with ddx5; self-association' region; the 'disordered' region

Full ESR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ESR1 p.Pro152Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
SYNE1 p.Arg8746Ter Pathogenic/Likely pathogenic ★★ same type
ESR1 p.Lys299Arg Uncertain significance ★★ ⚠ same type
SYNE1 p.Arg8735Leu Uncertain significance ★★ ⚠ same type
SYNE1 p.Arg8738His Uncertain significance ★★ ⚠ same type
SYNE1 p.Arg8746Gln Uncertain significance ★★ same type
SYNE1 p.Arg8782Gln Uncertain significance ★★ same type
SYNE1 p.Arg8782Gly 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/esr1-p-pro152 (accessed [today's date]).

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