Is MFF p.Pro71Leu (c.212C>T) pathogenic?

MFF p.Pro71Leu (c.212C>T) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.2896); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with MFF p.Pro71Leu (c.212C>T)?

MFF p.Pro71Leu (c.212C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MFF p.Pro71Leu (c.212C>T) in the general population?

MFF p.Pro71Leu (c.212C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about MFF p.Pro71Leu (c.212C>T)?

AlphaMissense predicts likely benign (score 0.2896) — an in-silico prediction, not a clinical call.

MFF p.Pro71Leu

c.212C>T · rs370366430 · VCV2603976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2896	likely benign
REVEL	0.492	indeterminate
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.49, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P97L vs ClinVar P71L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,834 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000372% 6/1,612,032 alleles · very rare exomes 2/1,459,932 · genomes 4/152,100 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,967
East Asian	0.00223%	44,802

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.Pro71Leu
Coding: c.212C>T
MANE Select: NM_001277062
dbSNP: rs370366430
Type: single nucleotide variant
Location: chr2:227332449 (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

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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-pro71leu (accessed [today's date]).

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