Is MTFMT p.Val83Met (c.247G>A) pathogenic?

MTFMT p.Val83Met (c.247G>A) is classified Uncertain significance in MTFMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely pathogenic (0.6951); Very rare (popmax 0.00167%, amr).

How common is MTFMT p.Val83Met (c.247G>A) in the general population?

MTFMT p.Val83Met (c.247G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MTFMT p.Val83Met (c.247G>A)?

AlphaMissense predicts likely pathogenic (score 0.6951) — an in-silico prediction, not a clinical call.

MTFMT p.Val83Met

c.247G>A · rs1358301355 · VCV1961017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6951	likely pathogenic
REVEL	0.727	pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,994 alleles

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

Overall 0.000186% 3/1,613,822 alleles · very rare exomes 2/1,461,678 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
European (non-Finnish)	0.00017%	589,929

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.Val83Met
Coding: c.247G>A
MANE Select: NM_139242
dbSNP: rs1358301355
Type: single nucleotide variant
Location: chr15:65027003 (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

Similar variants

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
MTFMT p.Ala213Thr Uncertain significance ★★ ⚠ same type
MTFMT p.Ala280Val Uncertain significance ★★ ⚠ 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-val83met (accessed [today's date]).

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