Is EI24 p.Leu86Phe (c.256C>T) pathogenic?

EI24 p.Leu86Phe (c.256C>T) is classified Uncertain significance in EI24 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.8548); Ultra-rare (popmax 0.0117%, amr).

How common is EI24 p.Leu86Phe (c.256C>T) in the general population?

EI24 p.Leu86Phe (c.256C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about EI24 p.Leu86Phe (c.256C>T)?

AlphaMissense predicts likely pathogenic (score 0.8548) — an in-silico prediction, not a clinical call.

EI24 p.Leu86Phe

c.256C>T · rs761501242 · VCV2325632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8548	likely pathogenic
REVEL	0.34	indeterminate
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 8,737 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,910 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,613,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,559
European (non-Finnish)	8.48e-05%	1,179,756

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: EI24
Protein: p.Leu86Phe
Coding: c.256C>T
MANE Select: NM_004879
dbSNP: rs761501242
Type: single nucleotide variant
Location: chr11:125577510 (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-leu86phe (accessed [today's date]).

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