Is ESR2 p.Ser283Arg (c.849C>A) pathogenic?

ESR2 p.Ser283Arg (c.849C>A) is classified Uncertain significance in ESR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.3375); Absent from gnomAD v4.1.

How common is ESR2 p.Ser283Arg (c.849C>A) in the general population?

ESR2 p.Ser283Arg (c.849C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESR2 p.Ser283Arg (c.849C>A)?

AlphaMissense predicts likely benign (score 0.3375) — an in-silico prediction, not a clinical call.

ESR2 p.Ser283Arg

c.849C>A · rs2550402707 · VCV3090545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3375 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3375	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -2.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.41, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 50 kb · p 0.43 · regional, not allelic
Overall
CADD	16.14	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ESR2
Protein: p.Ser283Arg
Coding: c.849C>A
MANE Select: NM_001437
dbSNP: rs2550402707
Type: single nucleotide variant
Location: chr14:64260552 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.76 · 39 PDB
Residue 283: the nr lbd domain

Full ESR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ESR2 p.Ala432Thr Uncertain significance ★★ ⚠ same type
ESR2 p.Arg230Gln Uncertain significance ★★ ⚠ same type
ESR2 p.Arg346Cys Uncertain significance ★★ ⚠ same type
ESR2 p.Arg388Gln Uncertain significance ★★ ⚠ same type
ESR2 p.Asn407Ser Uncertain significance ★★ ⚠ same type
ESR2 p.Asp154Asn Uncertain significance ★★ ⚠ same type
ESR2 p.Cys169Phe Uncertain significance ★★ ⚠ same type
ESR2 p.Gly243Asp 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/esr2-p-ser283arg (accessed [today's date]).

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