Is EI24 p.Trp83Arg (c.247T>C) pathogenic?

EI24 p.Trp83Arg (c.247T>C) is classified Uncertain significance in EI24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely pathogenic (0.9932); Absent from gnomAD v4.1.

How common is EI24 p.Trp83Arg (c.247T>C) in the general population?

EI24 p.Trp83Arg (c.247T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EI24 p.Trp83Arg (c.247T>C)?

AlphaMissense predicts likely pathogenic (score 0.9932) — an in-silico prediction, not a clinical call.

EI24 p.Trp83Arg

c.247T>C · VCV4017044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9932	likely pathogenic
REVEL	0.596	indeterminate
SaProt	LLR -10.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 8,737 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: EI24
Protein: p.Trp83Arg
Coding: c.247T>C
MANE Select: NM_004879
Type: single nucleotide variant
Location: chr11:125576313 (GRCh38)
Gene constraint: LOEUF 0.722 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.98

Full EI24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EI24 p.Ala45Thr Uncertain significance ★ ⚠ same type
EI24 p.Arg14Lys Uncertain significance ★ ⚠ same type
EI24 p.Arg44Lys Uncertain significance ★ ⚠ same type
EI24 p.Arg66Cys Uncertain significance ★ ⚠ same type
EI24 p.Arg66His Uncertain significance ★ ⚠ same type
EI24 p.Gln201Arg Uncertain significance ★ ⚠ same type
EI24 p.Ile26Val Uncertain significance ★ ⚠ same type
EI24 p.Leu183Ile 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/ei24-p-trp83arg (accessed [today's date]).

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