Is EI24 p.Leu205Phe (c.613C>T) pathogenic?

EI24 p.Leu205Phe (c.613C>T) is classified Uncertain significance in EI24 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.2134); Absent from gnomAD v4.1.

How common is EI24 p.Leu205Phe (c.613C>T) in the general population?

EI24 p.Leu205Phe (c.613C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EI24 p.Leu205Phe (c.613C>T)?

AlphaMissense predicts likely benign (score 0.2134) — an in-silico prediction, not a clinical call.

EI24 p.Leu205Phe

c.613C>T · rs767996205 · VCV3087825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2134 · 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	0.2134	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -7.53	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 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 8,737 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	21.0	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: EI24
Protein: p.Leu205Phe
Coding: c.613C>T
MANE Select: NM_004879
dbSNP: rs767996205
Type: single nucleotide variant
Location: chr11:125580144 (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-leu205phe (accessed [today's date]).

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