Is ELMO2 p.Arg28Trp (c.82C>T) pathogenic?

ELMO2 p.Arg28Trp (c.82C>T) is classified Uncertain significance in ELMO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: ambiguous (0.3994); Ultra-rare (popmax 0.055%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELMO2 p.Arg28Trp (c.82C>T)?

ELMO2 p.Arg28Trp (c.82C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ELMO2 p.Arg28Trp (c.82C>T) in the general population?

ELMO2 p.Arg28Trp (c.82C>T) is ultra-rare (popmax 0.055%, amr) (gnomAD).

What do computational predictors say about ELMO2 p.Arg28Trp (c.82C>T)?

AlphaMissense predicts ambiguous (score 0.3994) — an in-silico prediction, not a clinical call.

ELMO2 p.Arg28Trp

c.82C>T · VCV3844467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3994	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -12.27	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 27 kb · p 2.6e-31 · regional, not allelic
Overall
CADD	32.0	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 0.055% Admixed American · 33/59,984 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.00341% 55/1,613,436 alleles · ultra-rare exomes 27/1,461,274 · genomes 28/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.055%	1,818
African / African-American	0.00267%	37,452
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00153%	65,533
South Asian	0.0011%	91,032

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: ELMO2
Protein: p.Arg28Trp
Coding: c.82C>T
MANE Select: NM_133171
Type: single nucleotide variant
Location: chr20:46394086 (GRCh38)
Gene constraint: LOEUF 0.486 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 2 PDB

Full ELMO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELMO2 p.Asn490Lys Uncertain significance ★★ ⚠ same condition
ELMO2 p.Glu468Asp Uncertain significance ★★ ⚠ same condition
ELMO2 p.Ser396Gly Uncertain significance ★★ ⚠ same condition
ELMO2 p.Thr482Ala Uncertain significance ★★ ⚠ same condition
ELMO2 p.Ala235Thr Uncertain significance ★ ⚠ same condition
ELMO2 p.Ala246Ser Uncertain significance ★ ⚠ same condition
ELMO2 p.Ala333Gly Uncertain significance ★ ⚠ same condition
ELMO2 p.Ala467Thr Uncertain significance ★ ⚠ same condition

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/elmo2-p-arg28trp (accessed [today's date]).

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