Is LIMA1 p.Arg129= (c.385A>C) pathogenic?

LIMA1 p.Arg129= (c.385A>C) is classified Likely benign in LIMA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-10). Ultra-rare (popmax 0.0334%, afr); Associated with LIMA1-related disorder.

What condition is associated with LIMA1 p.Arg129= (c.385A>C)?

LIMA1 p.Arg129= (c.385A>C) is associated with LIMA1-related disorder (ClinVar).

How common is LIMA1 p.Arg129= (c.385A>C) in the general population?

LIMA1 p.Arg129= (c.385A>C) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

LIMA1 p.Arg129=

c.385A>C · rs375473793 · VCV3050485

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Conditions

LIMA1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 0.95
Overall
CADD	7.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 25/74,930 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00217% 35/1,614,072 alleles · ultra-rare exomes 18/1,461,894 · genomes 17/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0334%	2,997
Admixed American	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	8.47e-05%	1,180,044

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: LIMA1
Protein: p.Arg129=
Coding: c.385A>C
MANE Select: NM_016357
dbSNP: rs375473793
Type: single nucleotide variant
Location: chr12:50222266 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.12 · 1 PDB
Residue 129: the 'disordered' region

Full LIMA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LIMA1-related disorder

Similar variants

LIMA1 c.973-4G>T Likely benign same condition
LIMA1 p.Leu90= Likely benign same condition
LIMA1 p.Ala113Gly Uncertain significance ★ ⚠ same type
LIMA1 p.Ala136Val Uncertain significance ★ ⚠ same type
LIMA1 p.Ala183Asp Uncertain significance ★ ⚠ same type
LIMA1 p.Ala214Ser Uncertain significance ★ ⚠ same type
LIMA1 p.Ala367Val Uncertain significance ★ ⚠ same type
LIMA1 p.Ala479Val 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/lima1-p-arg129 (accessed [today's date]).

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