Is MTFMT p.His15Pro (c.44A>C) pathogenic?

MTFMT p.His15Pro (c.44A>C) is classified Uncertain significance in MTFMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-24). AlphaMissense: likely benign (0.0368); Very rare (popmax 0.00827%, eas); Associated with Inborn genetic diseases.

What condition is associated with MTFMT p.His15Pro (c.44A>C)?

MTFMT p.His15Pro (c.44A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MTFMT p.His15Pro (c.44A>C) in the general population?

MTFMT p.His15Pro (c.44A>C) is very rare (popmax 0.00827%, eas) (gnomAD).

What do computational predictors say about MTFMT p.His15Pro (c.44A>C)?

AlphaMissense predicts likely benign (score 0.0368) — an in-silico prediction, not a clinical call.

MTFMT p.His15Pro

c.44A>C · rs935174845 · VCV1919955

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0368 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00827%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0368	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -4.06	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 -0.24	GERP -2.3, phastCons 0.22
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	1.113	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00827% East Asian · 3/36,292 alleles

Filtering AF 0.00219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00111%

Overall 0.000466% 7/1,500,768 alleles · very rare exomes 6/1,348,718 · genomes 1/152,050 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00827%	12,097
Admixed American	0.00639%	15,647
South Asian	0.00125%	80,102

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.His15Pro
Coding: c.44A>C
MANE Select: NM_139242
dbSNP: rs935174845
Type: single nucleotide variant
Location: chr15:65029570 (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.His15Arg Uncertain significance ★★ ⚠ same residue
MTFMT p.His15Leu 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

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-his15pro (accessed [today's date]).

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