Is MFF p.Leu124= (c.372A>G) pathogenic?

MFF p.Leu124= (c.372A>G) is classified Likely benign in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2016-07-07). Very rare (popmax 0.000186%).

How common is MFF p.Leu124= (c.372A>G) in the general population?

MFF p.Leu124= (c.372A>G) is very rare (popmax 0.000186%) (gnomAD).

MFF p.Leu124=

c.372A>G · rs1057522742 · VCV387250

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000186%)

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 1.6	GERP -0.17, phastCons 1
Overall
CADD	8.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000186%

Overall 0.000186% 3/1,613,868 alleles · very rare exomes 3/1,461,570 · genomes 0/152,298 · joint denominator

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.Leu124=
Coding: c.372A>G
MANE Select: NM_001277062
dbSNP: rs1057522742
Type: single nucleotide variant
Location: chr2:227340312 (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

Similar variants

MFF p.Arg128Trp Uncertain significance ★★ ⚠ same type
MFF p.Arg136Cys Uncertain significance ★★ ⚠ same type
MFF p.Arg136His Uncertain significance ★★ ⚠ same type
MFF p.Arg199His Uncertain significance ★★ ⚠ same type
MFF p.Arg6Gln Uncertain significance ★★ ⚠ same type
MFF p.Arg92His Uncertain significance ★★ ⚠ same type
MFF p.Asp75Asn Uncertain significance ★★ ⚠ same type
MFF p.Gln52His 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/mff-p-leu124 (accessed [today's date]).

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