Is MTFMT p.Val5Ala (c.14T>C) pathogenic?

MTFMT p.Val5Ala (c.14T>C) is classified Benign in MTFMT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1316); Common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MTFMT p.Val5Ala (c.14T>C)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

MTFMT p.Val5Ala

Q: How common is MTFMT p.Val5Ala (c.14T>C) in the general population?

MTFMT p.Val5Ala (c.14T>C) is common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.14T>C · rs2946655 · VCV138269

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.79	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 0.53	GERP 0.029
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	7.08	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 13.4% African / African-American · 9,031/67,184 alleles

Filtering AF 13.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.1%

Overall 4.94% 70,630/1,428,416 alleles · common exomes 60,156/1,276,620 · genomes 10,474/151,796 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.4%	7
Finnishnot grpmax-eligible	7.03%	14
Amishnot grpmax-eligible	5.15%	19
Remaining individualsnot grpmax-eligible	4.7%	21
European (non-Finnish)	4.53%	22
South Asian	4.09%	24
Ashkenazi Jewishnot grpmax-eligible	4.09%	24
Admixed American	3.56%	28
Middle Eastern	3.2%	31
East Asian	2.93%	34

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.Val5Ala
Coding: c.14T>C
MANE Select: NM_139242
dbSNP: rs2946655
Type: single nucleotide variant
Location: chr15:65029600 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 5: a UniProt-annotated variant site (in)

Full MTFMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MTFMT p.Val5Met Uncertain significance ★ ⚠ same residue
MTFMT p.Val5= Likely benign ★ same residue
MTFMT c.722-2A>G Likely pathogenic ★★ same type
MTFMT p.Arg128Ter Pathogenic/Likely pathogenic ★★ same type
MTFMT p.Arg332Ter Pathogenic ★★ same type
MTFMT p.Ser125Leu Pathogenic/Likely pathogenic ★★ same type
MTFMT p.Ser209Leu Pathogenic ★★ ⚠ same type
MTFMT p.Trp9Ter Pathogenic ★★ same type

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-val5ala (accessed [today's date]).

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