Is LMOD2 p.Arg85Ser (c.255G>C) pathogenic?

LMOD2 p.Arg85Ser (c.255G>C) is classified Uncertain significance in LMOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely pathogenic (0.678); Ultra-rare (popmax 0.0135%, amr); Associated with Inborn genetic diseases.

What condition is associated with LMOD2 p.Arg85Ser (c.255G>C)?

LMOD2 p.Arg85Ser (c.255G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LMOD2 p.Arg85Ser (c.255G>C) in the general population?

LMOD2 p.Arg85Ser (c.255G>C) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about LMOD2 p.Arg85Ser (c.255G>C)?

AlphaMissense predicts likely pathogenic (score 0.678) — an in-silico prediction, not a clinical call.

LMOD2 p.Arg85Ser

c.255G>C · VCV4047827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.678 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.678	likely pathogenic
REVEL	0.212	benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -0.51, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 7,778 bp · p 0.09 · regional, not allelic
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% Admixed American · 8/59,328 alleles

Filtering AF 0.00668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00487%

Overall 0.000498% 8/1,607,792 alleles · ultra-rare exomes 7/1,455,658 · genomes 1/152,134 · 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: LMOD2
Protein: p.Arg85Ser
Coding: c.255G>C
MANE Select: NM_207163
Type: single nucleotide variant
Location: chr7:123656218 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14 · 6 PDB
Residue 85: the 'interaction with actin 1' region

Full LMOD2 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

LMOD2 p.Arg231Cys Uncertain significance ★★ ⚠ same condition
LMOD2 p.Glu276Lys Uncertain significance ★★ ⚠ same condition
LMOD2 p.Thr244Met Uncertain significance ★★ ⚠ same condition
LMOD2 p.Ala23Ser Uncertain significance ★ same condition
LMOD2 p.Ala23Val Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala287Pro Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala287Thr Uncertain significance ★ ⚠ same condition
LMOD2 p.Ala528Val 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/lmod2-p-arg85ser (accessed [today's date]).

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