Is ESR1 p.Arg157Ter (c.469C>T) pathogenic?

ESR1 p.Arg157Ter (c.469C>T) is classified Pathogenic in ESR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1994-10-20). Very rare (popmax 8.48e-05%, nfe); Associated with estrogen resistance syndrome.

What condition is associated with ESR1 p.Arg157Ter (c.469C>T)?

ESR1 p.Arg157Ter (c.469C>T) is associated with estrogen resistance syndrome (ClinVar).

How common is ESR1 p.Arg157Ter (c.469C>T) in the general population?

ESR1 p.Arg157Ter (c.469C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Estrogen resistance syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ESR1 p.Arg157Ter

c.469C>T · rs104893956 · VCV16592

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

estrogen resistance syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,766 alleles

Overall 6.84e-05% 1/1,461,216 alleles · very rare

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.Arg157Ter
Coding: c.469C>T
MANE Select: NM_000125
dbSNP: rs104893956
Type: single nucleotide variant
Location: chr6:151842613 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 492 PDB
Residue 157: 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

Disease context

estrogen resistance syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Estrogen resistance syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent

Similar variants

ESR1 p.Ser10= Benign ★★ same condition
ESR1 p.Thr594= Benign/Likely benign ★★ same condition
ESR1 c.453-351A>G Uncertain significance ★ same condition
ESR1 p.Gly145Ser Uncertain significance ★ ⚠ same condition
ESR1 p.Lys268Asn Uncertain significance ★ ⚠ same condition
ESR1 p.Arg394His Pathogenic/Likely pathogenic same condition
ESR1 p.Gln375His Pathogenic same condition
ESR1 p.Val364Glu Uncertain significance ⚠ 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/esr1-p-arg157ter (accessed [today's date]).

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