Is ELMO2 p.Thr150Pro (c.448A>C) pathogenic?

ELMO2 p.Thr150Pro (c.448A>C) is classified Uncertain significance in ELMO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely pathogenic (0.8807); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELMO2 p.Thr150Pro (c.448A>C)?

ELMO2 p.Thr150Pro (c.448A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ELMO2 p.Thr150Pro (c.448A>C) in the general population?

ELMO2 p.Thr150Pro (c.448A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELMO2 p.Thr150Pro (c.448A>C)?

AlphaMissense predicts likely pathogenic (score 0.8807) — an in-silico prediction, not a clinical call.

ELMO2 p.Thr150Pro

c.448A>C · rs2060066307 · VCV2534897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8807	likely pathogenic
REVEL	0.616	indeterminate
SaProt	LLR -10.86	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 27 kb · p 2.6e-31 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,986 alleles

Overall 0.000124% 2/1,613,830 alleles · very rare exomes 2/1,461,788 · genomes 0/152,042 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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.Thr150Pro
Coding: c.448A>C
MANE Select: NM_133171
dbSNP: rs2060066307
Type: single nucleotide variant
Location: chr20:46387415 (GRCh38)
Gene constraint: LOEUF 0.486 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 2 PDB
Residue 150: an α-helix

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-thr150pro (accessed [today's date]).

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