Is ELMOD2 p.Glu239Asp (c.717A>T) pathogenic?

ELMOD2 p.Glu239Asp (c.717A>T) is classified Uncertain significance in ELMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.1183); Ultra-rare (popmax 0.0366%, amr).

How common is ELMOD2 p.Glu239Asp (c.717A>T) in the general population?

ELMOD2 p.Glu239Asp (c.717A>T) is ultra-rare (popmax 0.0366%, amr) (gnomAD).

What do computational predictors say about ELMOD2 p.Glu239Asp (c.717A>T)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

ELMOD2 p.Glu239Asp

c.717A>T · rs150835853 · VCV2213746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0366%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -5.58	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 0.46	GERP -1.8, phastCons 0.83
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	15.08	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 0.0366% Admixed American · 20/54,690 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0202%

Overall 0.0101% 162/1,596,744 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0366%	2,734
Middle Eastern	0.0342%	2,926
Remaining individualsnot grpmax-eligible	0.013%	7,715
European (non-Finnish)	0.0109%	9,183
African / African-American	0.00405%	24,693
East Asian	0.00226%	44,310

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: ELMOD2
Protein: p.Glu239Asp
Coding: c.717A>T
MANE Select: NM_153702
dbSNP: rs150835853
Type: single nucleotide variant
Location: chr4:140543567 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.39
Residue 239: the elmo domain

Full ELMOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD2 c.142+43G>T Benign ★★ same type
ELMOD2 c.270-81T>G Benign ★★ same type
ELMOD2 c.-9-294A>G Benign ★★ same type
ELMOD2 c.*9C>T Benign/Likely benign ★★ same type
ELMOD2 p.Lys143Thr Benign/Likely benign ★★ same type
ELMOD2 p.Val39Gly Likely benign ★★ same type
ELMOD2 p.Arg167Ser Uncertain significance ★ ⚠ same type
ELMOD2 p.Asn183Ile 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/elmod2-p-glu239asp (accessed [today's date]).

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