Is LMF1 p.Phe409= (c.1227C>T) pathogenic?

LMF1 p.Phe409= (c.1227C>T) is classified Likely benign in LMF1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-04). Rare (popmax 0.118%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LMF1 p.Phe409= (c.1227C>T)?

LMF1 p.Phe409= (c.1227C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LMF1 p.Phe409= (c.1227C>T) in the general population?

LMF1 p.Phe409= (c.1227C>T) is rare (popmax 0.118%, eas) (gnomAD).

LMF1 p.Phe409=

c.1227C>T · rs199695197 · VCV1284280

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

Conditions

Cardiovascular phenotype

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 -6.2	GERP -3.8
Overall
CADD	0.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,870 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.0198% 319/1,612,760 alleles · rare exomes 297/1,460,462 · genomes 22/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	847
South Asian	0.0505%	1,980
Finnishnot grpmax-eligible	0.0413%	2,421
Remaining individualsnot grpmax-eligible	0.0208%	4,805
European (non-Finnish)	0.0149%	6,703
African / African-American	0.00666%	15,008

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.Phe409=
Coding: c.1227C>T
MANE Select: NM_022773
dbSNP: rs199695197
Type: single nucleotide variant
Location: chr16:870734 (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.Phe409Cys 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
LMF1 p.Ala499Val 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-phe409 (accessed [today's date]).

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