Is DNTTIP2 p.Phe26Ser (c.77T>C) pathogenic?

DNTTIP2 p.Phe26Ser (c.77T>C) is classified Likely benign in DNTTIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.056); Absent from gnomAD v4.1.

How common is DNTTIP2 p.Phe26Ser (c.77T>C) in the general population?

DNTTIP2 p.Phe26Ser (c.77T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNTTIP2 p.Phe26Ser (c.77T>C)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

DNTTIP2 p.Phe26Ser

c.77T>C · rs2525711066 · VCV3084871

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -2.96	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 1.7	GERP -1.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,294 bp · p 0.47 · regional, not allelic
Overall
CADD	15.62	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.Phe26Ser
Coding: c.77T>C
MANE Select: NM_014597
dbSNP: rs2525711066
Type: single nucleotide variant
Location: chr1:93877858 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.47 · 3 PDB
Residue 26: the 'disordered' region

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-phe26ser (accessed [today's date]).

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