Is MTFMT p.Pro11Leu (c.32C>T) pathogenic?

MTFMT p.Pro11Leu (c.32C>T) is classified Likely benign in MTFMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: likely benign (0.0929); Very rare (popmax 0.0041%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MTFMT p.Pro11Leu (c.32C>T)?

MTFMT p.Pro11Leu (c.32C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTFMT p.Pro11Leu (c.32C>T) in the general population?

MTFMT p.Pro11Leu (c.32C>T) is very rare (popmax 0.0041%, nfe) (gnomAD).

What do computational predictors say about MTFMT p.Pro11Leu (c.32C>T)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

MTFMT p.Pro11Leu

c.32C>T · rs993637538 · VCV2210992

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -4.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -1.1
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	5.37	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0041% European (non-Finnish) · 46/1,123,090 alleles

Filtering AF 0.00314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00281%

Overall 0.00314% 47/1,496,060 alleles · very rare exomes 46/1,343,956 · genomes 1/152,104 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0041%	24,415
African / African-American	0.00145%	68,924

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: MTFMT
Protein: p.Pro11Leu
Coding: c.32C>T
MANE Select: NM_139242
dbSNP: rs993637538
Type: single nucleotide variant
Location: chr15:65029582 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.08

Full MTFMT 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

MTFMT p.Pro11Ser Uncertain significance ★ ⚠ same residue
MTFMT p.Ala280Val Uncertain significance ★★ ⚠ same condition
MTFMT p.Ala383Gly Uncertain significance ★★ ⚠ same condition
MTFMT p.Arg154His Uncertain significance ★★ ⚠ same condition
MTFMT p.Arg21Thr Uncertain significance ★★ ⚠ same condition
MTFMT p.Arg31Pro Uncertain significance ★★ ⚠ same condition
MTFMT p.Arg371Lys Uncertain significance ★★ ⚠ same condition
MTFMT p.Glu259Gly 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/mtfmt-p-pro11leu (accessed [today's date]).

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