Is MFF p.Ala72Thr (c.214G>A) pathogenic?

MFF p.Ala72Thr (c.214G>A) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MFF p.Ala72Thr (c.214G>A)?

MFF p.Ala72Thr (c.214G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MFF p.Ala72Thr (c.214G>A) in the general population?

MFF p.Ala72Thr (c.214G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MFF p.Ala72Thr (c.214G>A)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

MFF p.Ala72Thr

c.214G>A · VCV4624935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	23.7	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 A98T vs ClinVar A72T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,160 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,008 alleles · very rare exomes 2/1,459,886 · genomes 0/152,122 · 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.Ala72Thr
Coding: c.214G>A
MANE Select: NM_001277062
Type: single nucleotide variant
Location: chr2:227332451 (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-ala72thr (accessed [today's date]).

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