Is DNTTIP2 p.Asn659Lys (c.1977T>G) pathogenic?

DNTTIP2 p.Asn659Lys (c.1977T>G) is classified Uncertain significance in DNTTIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.8199); Absent from gnomAD v4.1.

How common is DNTTIP2 p.Asn659Lys (c.1977T>G) in the general population?

DNTTIP2 p.Asn659Lys (c.1977T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNTTIP2 p.Asn659Lys (c.1977T>G)?

AlphaMissense predicts likely pathogenic (score 0.8199) — an in-silico prediction, not a clinical call.

DNTTIP2 p.Asn659Lys

c.1977T>G · VCV4014002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8199 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8199	likely pathogenic
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -3.5, phastCons 0.084
Regional constraint	o/e 1.02	unconstrained · MANE · 9,294 bp · p 0.47 · regional, not allelic
Overall
CADD	21.3	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: DNTTIP2
Protein: p.Asn659Lys
Coding: c.1977T>G
MANE Select: NM_014597
Type: single nucleotide variant
Location: chr1:93872162 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.47 · 3 PDB
Residue 659: an α-helix

Full DNTTIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNTTIP2 p.Ala11Thr Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala347Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala358Pro Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Ser Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Thr Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala43Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala511Val Uncertain significance ★ ⚠ same type
DNTTIP2 p.Ala554Val 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/dnttip2-p-asn659lys (accessed [today's date]).

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