Is DNTTIP2 p.Asn285Ser (c.854A>G) pathogenic?

DNTTIP2 p.Asn285Ser (c.854A>G) is classified Likely benign in DNTTIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0639); Very rare (popmax 0.00667%, afr).

How common is DNTTIP2 p.Asn285Ser (c.854A>G) in the general population?

DNTTIP2 p.Asn285Ser (c.854A>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DNTTIP2 p.Asn285Ser (c.854A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

DNTTIP2 p.Asn285Ser

c.854A>G · VCV4661594

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.53	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 -8	GERP -3.2
Regional constraint	o/e 1.02	unconstrained · MANE · 9,294 bp · p 0.47 · regional, not allelic
Overall
CADD	0.001	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 0.00667% African / African-American · 5/74,940 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000931% 15/1,611,716 alleles · very rare exomes 11/1,459,506 · genomes 4/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,988
Remaining individualsnot grpmax-eligible	0.0016%	62,444
South Asian	0.0011%	91,078
European (non-Finnish)	0.000678%	147,472

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: DNTTIP2
Protein: p.Asn285Ser
Coding: c.854A>G
MANE Select: NM_014597
Type: single nucleotide variant
Location: chr1:93877081 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.47 · 3 PDB

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-asn285ser (accessed [today's date]).

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