Is ELMO2 p.Asp660= (c.1980T>C) pathogenic?

ELMO2 p.Asp660= (c.1980T>C) is classified Benign in ELMO2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-28). Common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with primary intraosseous venous malformation.

What condition is associated with ELMO2 p.Asp660= (c.1980T>C)?

ELMO2 p.Asp660= (c.1980T>C) is associated with primary intraosseous venous malformation (ClinVar).

How is Familial intraosseous vascular malformation inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ELMO2 p.Asp660=

Q: How common is ELMO2 p.Asp660= (c.1980T>C) in the general population?

ELMO2 p.Asp660= (c.1980T>C) is common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1980T>C · rs2257495 · VCV1236006

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 100%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

primary intraosseous venous malformation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.7
Overall
CADD	0.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% European (non-Finnish) · 1,179,255/1,179,362 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.7% 1,608,171/1,612,608 alleles · common exomes 1,458,216/1,460,384 · genomes 149,955/152,224 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
European (non-Finnish)grpmax	100%	1
East Asian	100%	1
South Asian	100%	1
Middle Eastern	100%	1
Remaining individualsnot grpmax-eligible	99.7%	1
Admixed American	99.6%	1
African / African-American	94.8%	1

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp660=
Coding: c.1980T>C
MANE Select: NM_133171
dbSNP: rs2257495
Type: single nucleotide variant
Location: chr20:46367543 (GRCh38)
Gene constraint: LOEUF 0.486 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 2 PDB
Residue 660: the ph domain

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

Disease context

primary intraosseous venous malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial intraosseous vascular malformation (Orphanet):

Inheritance: Autosomal recessive

Similar variants

ELMO2 p.Arg478Gln Uncertain significance ★★ ⚠ same condition
ELMO2 p.Glu468Asp Uncertain significance ★★ ⚠ same condition
ELMO2 p.Ser396Gly Uncertain significance ★★ ⚠ same condition
ELMO2 p.Arg321= Benign ★★ same condition
ELMO2 p.Leu378= Benign/Likely benign ★★ same condition
ELMO2 c.1065+1G>T Pathogenic ★ same condition
ELMO2 c.1802-1G>C Likely pathogenic ★ same condition
ELMO2 p.Arg483Ter Likely pathogenic ★ 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-asp660 (accessed [today's date]).

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