Is MTF1 p.Pro445Ser (c.1333C>T) pathogenic?

MTF1 p.Pro445Ser (c.1333C>T) is classified Likely benign in MTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0911); Rare (popmax 0.528%, afr).

How common is MTF1 p.Pro445Ser (c.1333C>T) in the general population?

MTF1 p.Pro445Ser (c.1333C>T) is rare (popmax 0.528%, afr) (gnomAD).

What do computational predictors say about MTF1 p.Pro445Ser (c.1333C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

MTF1 p.Pro445Ser

c.1333C>T · rs9729276 · VCV719703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.528%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.70	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 3.2	GERP 0.87, phastCons 1
Overall
CADD	17.28	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 0.528% African / African-American · 396/75,024 alleles

Filtering AF 0.485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0276% 446/1,614,122 alleles · rare exomes 220/1,461,826 · genomes 226/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.528%	189
Admixed American	0.0433%	2,309
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000339%	295,005

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: MTF1
Protein: p.Pro445Ser
Coding: c.1333C>T
MANE Select: NM_005955
dbSNP: rs9729276
Type: single nucleotide variant
Location: chr1:37822555 (GRCh38)
Structure: AlphaFold pLDDT 89.80 · 1 PDB
Residue 445: the transferrin-like 2 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-pro445ser (accessed [today's date]).

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