Is DNTT p.Met44Val (c.130A>G) pathogenic?

DNTT p.Met44Val (c.130A>G) is classified Uncertain significance in DNTT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: ambiguous (0.5519); Absent from gnomAD v4.1.

How common is DNTT p.Met44Val (c.130A>G) in the general population?

DNTT p.Met44Val (c.130A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNTT p.Met44Val (c.130A>G)?

AlphaMissense predicts ambiguous (score 0.5519) — an in-silico prediction, not a clinical call.

DNTT p.Met44Val

c.130A>G · VCV4835871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5519	ambiguous
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -6.05	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 34 kb · p 0.13 · regional, not allelic
Overall
CADD	23.3	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

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: DNTT
Protein: p.Met44Val
Coding: c.130A>G
MANE Select: NM_004088
Type: single nucleotide variant
Location: chr10:96304627 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.49 · 2 PDB
Residue 44: the brct domain; a turn

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

Similar variants

DNTT c.203+7C>G Benign ★★ same type
DNTT c.203+9G>A Benign ★★ same type
DNTT p.Ala90Val Benign ★★ same type
DNTT p.Asp280His Likely benign ★★ ⚠ same type
DNTT p.Glu244= Benign/Likely benign ★★ same type
DNTT p.Ala194Val Uncertain significance ★ ⚠ same type
DNTT p.Ala195Thr Uncertain significance ★ ⚠ same type
DNTT p.Ala21Val 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/dntt-p-met44val (accessed [today's date]).

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