Is ELMOD2 p.Thr185Pro (c.553A>C) pathogenic?

ELMOD2 p.Thr185Pro (c.553A>C) is classified Uncertain significance in ELMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.057); Very rare (popmax 0.00068%, nfe).

How common is ELMOD2 p.Thr185Pro (c.553A>C) in the general population?

ELMOD2 p.Thr185Pro (c.553A>C) is very rare (popmax 0.00068%, nfe) (gnomAD).

What do computational predictors say about ELMOD2 p.Thr185Pro (c.553A>C)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

ELMOD2 p.Thr185Pro

c.553A>C · VCV3508002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00068%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP -0.64, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	24.0	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 0.00068% European (non-Finnish) · 8/1,175,786 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000498% 8/1,606,064 alleles · very rare exomes 6/1,454,066 · genomes 2/151,998 · joint denominator

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.Thr185Pro
Coding: c.553A>C
MANE Select: NM_153702
Type: single nucleotide variant
Location: chr4:140542593 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.39
Residue 185: 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-thr185pro (accessed [today's date]).

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