Is ELMOD3 p.Glu236Lys (c.706G>A) pathogenic?

ELMOD3 p.Glu236Lys (c.706G>A) is classified Likely benign in ELMOD3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-19). AlphaMissense: likely benign (0.2427); Rare (popmax 0.491%, eas).

How common is ELMOD3 p.Glu236Lys (c.706G>A) in the general population?

ELMOD3 p.Glu236Lys (c.706G>A) is rare (popmax 0.491%, eas) (gnomAD).

What do computational predictors say about ELMOD3 p.Glu236Lys (c.706G>A)?

AlphaMissense predicts likely benign (score 0.2427) — an in-silico prediction, not a clinical call.

ELMOD3 p.Glu236Lys

c.706G>A · rs75956808 · VCV500138

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2427 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.491%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2427	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -11.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	25.2	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 0.491% East Asian · 218/44,436 alleles

Filtering AF 0.437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.417%

Overall 0.0252% 406/1,609,722 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.491%	204
Ashkenazi Jewishnot grpmax-eligible	0.308%	325
Remaining individualsnot grpmax-eligible	0.069%	1,450
South Asian	0.0255%	3,922
Admixed American	0.0118%	8,500
European (non-Finnish)	0.00195%	51,216
African / African-American	0.00134%	74,768

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: ELMOD3
Protein: p.Glu236Lys
Coding: c.706G>A
MANE Select: NM_001135022
dbSNP: rs75956808
Type: single nucleotide variant
Location: chr2:85377442 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18
Residue 236: the elmo domain

Full ELMOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD3 p.Ala234Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala289Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala38Thr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Gln100Ter Uncertain significance ★★ same type
ELMOD3 p.Gln371Ter Uncertain significance ★★ same type
ELMOD3 p.His294Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.His297Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Leu164Met 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/elmod3-p-glu236lys (accessed [today's date]).

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