Is ELMOD1 p.Lys225Thr (c.674A>C) pathogenic?

ELMOD1 p.Lys225Thr (c.674A>C) is classified Uncertain significance in ELMOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: likely benign (0.1653); Absent from gnomAD v4.1.

How common is ELMOD1 p.Lys225Thr (c.674A>C) in the general population?

ELMOD1 p.Lys225Thr (c.674A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELMOD1 p.Lys225Thr (c.674A>C)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

ELMOD1 p.Lys225Thr

c.674A>C · VCV3844483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0031 · regional, not allelic
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELMOD1
Protein: p.Lys225Thr
Coding: c.674A>C
MANE Select: NM_018712
Type: single nucleotide variant
Location: chr11:107654198 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.80
Residue 225: the elmo domain

Full ELMOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD1 p.Ala117Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala188Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala221Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala231Pro Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala326Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala76Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg113Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg123Leu 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/elmod1-p-lys225thr (accessed [today's date]).

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