Is LMOD3 p.Phe274Ser (c.821T>C) pathogenic?

LMOD3 p.Phe274Ser (c.821T>C) is classified Uncertain significance in LMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely pathogenic (0.9611); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LMOD3 p.Phe274Ser (c.821T>C)?

LMOD3 p.Phe274Ser (c.821T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD3 p.Phe274Ser (c.821T>C) in the general population?

LMOD3 p.Phe274Ser (c.821T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LMOD3 p.Phe274Ser (c.821T>C)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

LMOD3 p.Phe274Ser

c.821T>C · rs1487439846 · VCV2382851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic · top 6% in LMOD3
REVEL	0.517	indeterminate
SaProt	LLR -12.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.0038 · regional, not allelic
Overall
CADD	25.8	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

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: LMOD3
Protein: p.Phe274Ser
Coding: c.821T>C
MANE Select: NM_198271
dbSNP: rs1487439846
Type: single nucleotide variant
Location: chr3:69119534 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79

Full LMOD3 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

LMOD3 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
LMOD3 p.Ala475Thr Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg111Cys Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg171Gly Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg307His Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg479Gly Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg486Gly Uncertain significance ★★ ⚠ same condition
LMOD3 p.Arg495Ser 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/lmod3-p-phe274ser (accessed [today's date]).

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