Is MFF p.Ala34Val (c.101C>T) pathogenic?

MFF p.Ala34Val (c.101C>T) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.1015); Very rare (popmax 0.00333%, amr).

How common is MFF p.Ala34Val (c.101C>T) in the general population?

MFF p.Ala34Val (c.101C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MFF p.Ala34Val (c.101C>T)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

MFF p.Ala34Val

c.101C>T · rs766707640 · VCV2821968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1015	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	22.7	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 A60V vs ClinVar A34V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,032 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,220 alleles · very rare exomes 2/1,461,884 · genomes 0/152,336 · 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.Ala34Val
Coding: c.101C>T
MANE Select: NM_001277062
dbSNP: rs766707640
Type: single nucleotide variant
Location: chr2:227330766 (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

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MFF p.Arg199His Uncertain significance ★★ ⚠ same type
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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-ala34val (accessed [today's date]).

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