Is MTF1 p.Cys207Phe (c.620G>T) pathogenic?

MTF1 p.Cys207Phe (c.620G>T) is classified Uncertain significance in MTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1.

How common is MTF1 p.Cys207Phe (c.620G>T) in the general population?

MTF1 p.Cys207Phe (c.620G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTF1 p.Cys207Phe (c.620G>T)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

MTF1 p.Cys207Phe

c.620G>T · rs2524635251 · VCV2292232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 1% in MTF1
REVEL	0.925	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	33.0	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

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.Cys207Phe
Coding: c.620G>T
MANE Select: NM_005955
dbSNP: rs2524635251
Type: single nucleotide variant
Location: chr1:37839947 (GRCh38)
Structure: AlphaFold pLDDT 89.80 · 1 PDB
Residue 207: the transferrin-like 1 domain

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-cys207phe (accessed [today's date]).

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