Is EI24 p.Pro248Ser (c.742C>T) pathogenic?

EI24 p.Pro248Ser (c.742C>T) is classified Likely pathogenic in EI24 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9877); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with EI24 p.Pro248Ser (c.742C>T)?

EI24 p.Pro248Ser (c.742C>T) is associated with intellectual disability (ClinVar).

How common is EI24 p.Pro248Ser (c.742C>T) in the general population?

EI24 p.Pro248Ser (c.742C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EI24 p.Pro248Ser (c.742C>T)?

AlphaMissense predicts likely pathogenic (score 0.9877) — an in-silico prediction, not a clinical call.

EI24 p.Pro248Ser

c.742C>T · rs1938981293 · VCV996579

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9877	likely pathogenic ✓ concordant with ClinVar
REVEL	0.748	pathogenic-leaning
SaProt	LLR -13.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 1,150 bp · p 1.9e-07 · regional, not allelic
Overall
CADD	24.5	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

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.Pro248Ser
Coding: c.742C>T
MANE Select: NM_004879
dbSNP: rs1938981293
Type: single nucleotide variant
Location: chr11:125581279 (GRCh38)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro248ser (accessed [today's date]).

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