Is DMTF1 p.Val19Leu (c.55G>C) pathogenic?

DMTF1 p.Val19Leu (c.55G>C) is classified Uncertain significance in DMTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: ambiguous (0.3704); Very rare (popmax 0.00168%, amr).

How common is DMTF1 p.Val19Leu (c.55G>C) in the general population?

DMTF1 p.Val19Leu (c.55G>C) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about DMTF1 p.Val19Leu (c.55G>C)?

AlphaMissense predicts ambiguous (score 0.3704) — an in-silico prediction, not a clinical call.

DMTF1 p.Val19Leu

c.55G>C · VCV3502754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3704	ambiguous
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 8,650 bp · p 0.97 · regional, not allelic
Overall
CADD	22.6	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 0.00168% Admixed American · 1/59,584 alleles

Overall 0.000657% 1/152,184 alleles · very rare

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: DMTF1
Protein: p.Val19Leu
Coding: c.55G>C
MANE Select: NM_001142327
Type: single nucleotide variant
Location: chr7:87164996 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.72 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 19: the 'interaction with ccnd2' region

Full DMTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMTF1 p.Val19Met Uncertain significance ★ ⚠ same residue
DMP1 p.Gly135Ter Pathogenic/Likely pathogenic ★★ same type
DMP1 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
DMP1 c.*159T>A Uncertain significance ★★ same type
DMP1 c.*77T>C Uncertain significance ★★ same type
DMP1 p.Arg173Trp Uncertain significance ★★ ⚠ same type
DMP1 p.Arg302Ile Uncertain significance ★★ ⚠ same type
DMP1 p.Arg310Lys 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/dmtf1-p-val19leu (accessed [today's date]).

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