Is LMF1 p.Pro554= (c.1662C>G) pathogenic?

LMF1 p.Pro554= (c.1662C>G) is classified Likely benign in LMF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-30). Very rare (popmax 0.00504%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LMF1 p.Pro554= (c.1662C>G)?

LMF1 p.Pro554= (c.1662C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is LMF1 p.Pro554= (c.1662C>G) in the general population?

LMF1 p.Pro554= (c.1662C>G) is very rare (popmax 0.00504%, amr) (gnomAD).

LMF1 p.Pro554=

c.1662C>G · rs913911840 · VCV1536038

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00504%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP -3.1, phastCons 0.17
Overall
CADD	2.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00504% Admixed American · 3/59,488 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000671%

Overall 0.000311% 5/1,608,186 alleles · very rare exomes 4/1,456,062 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00504%	19,829
Remaining individualsnot grpmax-eligible	0.00161%	62,272
European (non-Finnish)	8.48e-05%	1,178,906

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.Pro554=
Coding: c.1662C>G
MANE Select: NM_022773
dbSNP: rs913911840
Type: single nucleotide variant
Location: chr16:854574 (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.Pro554Leu 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-pro554 (accessed [today's date]).

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