Is MTFMT p.Val291Phe (c.871G>T) pathogenic?

MTFMT p.Val291Phe (c.871G>T) is classified Uncertain significance in MTFMT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1837); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTFMT p.Val291Phe (c.871G>T)?

MTFMT p.Val291Phe (c.871G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTFMT p.Val291Phe (c.871G>T) in the general population?

MTFMT p.Val291Phe (c.871G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTFMT p.Val291Phe (c.871G>T)?

AlphaMissense predicts likely benign (score 0.1837) — an in-silico prediction, not a clinical call.

MTFMT p.Val291Phe

c.871G>T · rs2506149774 · VCV3214685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1837	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -11.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.35	donor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MTFMT
Protein: p.Val291Phe
Coding: c.871G>T
MANE Select: NM_139242
dbSNP: rs2506149774
Type: single nucleotide variant
Location: chr15:65006134 (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.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
MTFMT p.Gly33Asp 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-val291phe (accessed [today's date]).

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