Is LMF1 p.Pro86= (c.258C>A) pathogenic?

LMF1 p.Pro86= (c.258C>A) is classified Likely benign in LMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). Ultra-rare (popmax 0.033%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LMF1 p.Pro86= (c.258C>A)?

LMF1 p.Pro86= (c.258C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is LMF1 p.Pro86= (c.258C>A) in the general population?

LMF1 p.Pro86= (c.258C>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

LMF1 p.Pro86=

c.258C>A · rs1839340851 · VCV1793477

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.71	GERP -0.59, phastCons 1
Overall
CADD	1.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,054 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000683% 11/1,611,286 alleles · ultra-rare exomes 11/1,458,912 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.00481%	20,795
European (non-Finnish)	0.000509%	196,360

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: LMF1
Protein: p.Pro86=
Coding: c.258C>A
MANE Select: NM_022773
dbSNP: rs1839340851
Type: single nucleotide variant
Location: chr16:954602 (GRCh38)
Gene constraint: LOEUF 1.436 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49

Full LMF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LMF1 p.Pro86His Uncertain significance ★ ⚠ same residue
LMF1 p.Pro86Leu Uncertain significance ★ ⚠ same residue
LMF1 p.Arg233Ter Pathogenic/Likely pathogenic ★★ same condition
LMF1 p.Gln299Ter Pathogenic/Likely pathogenic ★★ same condition
LMF1 p.Ala252Val Uncertain significance ★★ same condition
LMF1 p.Ala429Val Uncertain significance ★★ ⚠ same condition
LMF1 p.Ala469Val Uncertain significance ★★ ⚠ same condition
LMF1 p.Ala494Gly 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/lmf1-p-pro86 (accessed [today's date]).

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