Is MTF1 p.Ser366= (c.1098A>G) pathogenic?

MTF1 p.Ser366= (c.1098A>G) is classified Likely benign in MTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-10). Absent from gnomAD v4.1.

How common is MTF1 p.Ser366= (c.1098A>G) in the general population?

MTF1 p.Ser366= (c.1098A>G) is absent from gnomAD v4.1 (gnomAD).

MTF1 p.Ser366=

c.1098A>G · VCV4966449

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.39, phastCons 1
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

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: MTF1
Protein: p.Ser366=
Coding: c.1098A>G
MANE Select: NM_005955
Type: single nucleotide variant
Location: chr1:37823783 (GRCh38)
Structure: AlphaFold pLDDT 89.80 · 1 PDB
Residue 366: the transferrin-like 2 domain; a β-strand

Full MTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MELTF p.Val55Ile Benign ★★ same type
MTF1 p.Thr228= Likely benign ★★ same type
MTF1 p.Thr364Ile Likely benign ★★ same type
MELTF p.Ala699Val Uncertain significance ★ ⚠ same type
MELTF p.Arg215Trp Uncertain significance ★ ⚠ same type
MELTF p.Arg275Gln Uncertain significance ★ ⚠ same type
MELTF p.Asn135Ser Uncertain significance ★ ⚠ same type
MELTF p.Gln540Arg 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/mtf1-p-ser366 (accessed [today's date]).

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