Is DNTT p.Ala239Ser (c.715G>T) pathogenic?

DNTT p.Ala239Ser (c.715G>T) is classified Uncertain significance in DNTT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0789%, amr).

How common is DNTT p.Ala239Ser (c.715G>T) in the general population?

DNTT p.Ala239Ser (c.715G>T) is ultra-rare (popmax 0.0789%, amr) (gnomAD).

What do computational predictors say about DNTT p.Ala239Ser (c.715G>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

DNTT p.Ala239Ser

c.715G>T · VCV4243698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0789%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.23	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 5.9	GERP -0.006, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 34 kb · p 0.13 · regional, not allelic
Overall
CADD	18.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0789% Admixed American · 47/59,550 alleles

Filtering AF 0.061% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0546%

Overall 0.00293% 47/1,602,654 alleles · ultra-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: DNTT
Protein: p.Ala239Ser
Coding: c.715G>T
MANE Select: NM_004088
Type: single nucleotide variant
Location: chr10:96322693 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.49 · 2 PDB
Residue 239: the 'mediates interaction with dnttip2' region

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-ala239ser (accessed [today's date]).

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