Is MTF1 p.Pro440Ser (c.1318C>T) pathogenic?

MTF1 p.Pro440Ser (c.1318C>T) is classified Benign in MTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-01). AlphaMissense: likely benign (0.0895); Low-frequency (popmax 1.52%, afr).

How common is MTF1 p.Pro440Ser (c.1318C>T) in the general population?

MTF1 p.Pro440Ser (c.1318C>T) is low-frequency (popmax 1.52%, afr) (gnomAD).

What do computational predictors say about MTF1 p.Pro440Ser (c.1318C>T)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

MTF1 p.Pro440Ser

c.1318C>T · rs61734999 · VCV769238

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.87	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 3.3	GERP -1.4, phastCons 1
Overall
CADD	15.02	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 1.52% African / African-American · 1,144/75,020 alleles

Filtering AF 1.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.42%

Overall 0.0782% 1,262/1,614,064 alleles · low-frequency exomes 595/1,461,816 · genomes 667/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.52%	66
Middle Eastern	0.0825%	1,212
Admixed American	0.0817%	1,225
Remaining individualsnot grpmax-eligible	0.0816%	1,226
South Asian	0.0022%	45,540
European (non-Finnish)	0.000932%	107,274

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.Pro440Ser
Coding: c.1318C>T
MANE Select: NM_005955
dbSNP: rs61734999
Type: single nucleotide variant
Location: chr1:37822570 (GRCh38)
Structure: AlphaFold pLDDT 89.80 · 1 PDB
Residue 440: 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-pro440ser (accessed [today's date]).

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