Is EI24 p.Arg44Lys (c.131G>A) pathogenic?

EI24 p.Arg44Lys (c.131G>A) is classified Uncertain significance in EI24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely benign (0.1024); Ultra-rare (popmax 0.0497%, sas).

How common is EI24 p.Arg44Lys (c.131G>A) in the general population?

EI24 p.Arg44Lys (c.131G>A) is ultra-rare (popmax 0.0497%, sas) (gnomAD).

What do computational predictors say about EI24 p.Arg44Lys (c.131G>A)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

EI24 p.Arg44Lys

c.131G>A · VCV4017043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.35, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 8,737 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0497% South Asian · 43/86,600 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0337%

Overall 0.00315% 50/1,587,812 alleles · ultra-rare exomes 47/1,435,498 · genomes 3/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0497%	2,014
Remaining individualsnot grpmax-eligible	0.00487%	20,543
Admixed American	0.00358%	27,912
European (non-Finnish)	0.000171%	583,591

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.Arg44Lys
Coding: c.131G>A
MANE Select: NM_004879
Type: single nucleotide variant
Location: chr11:125575351 (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.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
EI24 p.Leu205Phe 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-arg44lys (accessed [today's date]).

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