Is MFF p.Leu147= (c.441T>A) pathogenic?

MFF p.Leu147= (c.441T>A) is classified Likely benign in MFF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-29). Ultra-rare (popmax 0.0626%, afr); Associated with Inborn genetic diseases.

What condition is associated with MFF p.Leu147= (c.441T>A)?

MFF p.Leu147= (c.441T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MFF p.Leu147= (c.441T>A) in the general population?

MFF p.Leu147= (c.441T>A) is ultra-rare (popmax 0.0626%, afr) (gnomAD).

MFF p.Leu147=

c.441T>A · VCV3395455

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, afr)

Conditions

Inborn genetic diseases

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 2.4	GERP -0.19, phastCons 1
Overall
CADD	12.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% African / African-American · 47/75,022 alleles

Filtering AF 0.0483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00316% 51/1,613,490 alleles · ultra-rare exomes 26/1,461,166 · genomes 25/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0626%	1,596
Admixed American	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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: MFF
Protein: p.Leu147=
Coding: c.441T>A
MANE Select: NM_001277062
Type: single nucleotide variant
Location: chr2:227347226 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 64.74

Full MFF 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

MFF p.Arg128Trp Uncertain significance ★★ ⚠ same condition
MFF p.Arg136His Uncertain significance ★★ ⚠ same condition
MFF p.Arg6Gln Uncertain significance ★★ ⚠ same condition
MFF p.Arg92His Uncertain significance ★★ ⚠ same condition
MFF p.Gln52His Uncertain significance ★★ ⚠ same condition
MFF p.His215Pro Uncertain significance ★★ ⚠ same condition
MFF p.Ile230Thr Uncertain significance ★★ ⚠ same condition
MFF p.Ile250Ser 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/mff-p-leu147 (accessed [today's date]).

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