Is ELMOD3 p.Thr183= (c.549C>T) pathogenic?

ELMOD3 p.Thr183= (c.549C>T) is classified Benign in ELMOD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 6.8%, mid) — too common for a highly-penetrant pathogenic allele.

ELMOD3 p.Thr183=

Q: How common is ELMOD3 p.Thr183= (c.549C>T) in the general population?

ELMOD3 p.Thr183= (c.549C>T) is common (popmax 6.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.549C>T · rs115378987 · VCV509057

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.8%, mid) — too common for a highly-penetrant pathogenic allele

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 -12	GERP -5.4
Overall
CADD	0.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.8% Middle Eastern · 412/6,058 alleles

Filtering AF 6.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.05%

Overall 2.18% 35,129/1,614,142 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	7.01%	14
Middle Easterngrpmax	6.8%	15
Amishnot grpmax-eligible	4.06%	25
Remaining individualsnot grpmax-eligible	2.37%	42
Finnishnot grpmax-eligible	2.27%	44
European (non-Finnish)	2.23%	45
Admixed American	2.07%	48
South Asian	1.96%	51
African / African-American	0.473%	211
East Asian	0.0134%	7,479

Ashkenazi Jewish 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: ELMOD3
Protein: p.Thr183=
Coding: c.549C>T
MANE Select: NM_001135022
dbSNP: rs115378987
Type: single nucleotide variant
Location: chr2:85371504 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18
Residue 183: the elmo domain

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

Similar variants

ELMOD3 p.Thr183Ile Uncertain significance ★★ ⚠ same residue
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

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-thr183 (accessed [today's date]).

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