Is MTFMT p.Ile283Val (c.847A>G) pathogenic?

MTFMT p.Ile283Val (c.847A>G) is classified Benign/Likely benign in MTFMT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.0579); Rare (popmax 0.614%, afr).

How common is MTFMT p.Ile283Val (c.847A>G) in the general population?

MTFMT p.Ile283Val (c.847A>G) is rare (popmax 0.614%, afr) (gnomAD).

What do computational predictors say about MTFMT p.Ile283Val (c.847A>G)?

AlphaMissense predicts likely benign (score 0.0579) — an in-silico prediction, not a clinical call.

MTFMT p.Ile283Val

c.847A>G · rs114097513 · VCV724265

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0579 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.614%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0579	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.94	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 -3	GERP -0.58
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	2.896	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 0.614% African / African-American · 461/75,030 alleles

Filtering AF 0.568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.55%

Overall 0.0315% 508/1,612,944 alleles · rare exomes 243/1,460,616 · genomes 265/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.614%	163
Remaining individualsnot grpmax-eligible	0.04%	2,497
Admixed American	0.0267%	3,750
European (non-Finnish)	0.000509%	196,552

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.Ile283Val
Coding: c.847A>G
MANE Select: NM_139242
dbSNP: rs114097513
Type: single nucleotide variant
Location: chr15:65006158 (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-ile283val (accessed [today's date]).

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