Is DNTT p.Arg48Ser (c.142C>A) pathogenic?

DNTT p.Arg48Ser (c.142C>A) is classified Uncertain significance in DNTT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.9626); Very rare (popmax 0.00356%, nfe).

How common is DNTT p.Arg48Ser (c.142C>A) in the general population?

DNTT p.Arg48Ser (c.142C>A) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about DNTT p.Arg48Ser (c.142C>A)?

AlphaMissense predicts likely pathogenic (score 0.9626) — an in-silico prediction, not a clinical call.

DNTT p.Arg48Ser

c.142C>A · rs779136442 · VCV3084844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9626	likely pathogenic · top 3% in DNTT
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -11.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 34 kb · p 0.13 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00356% European (non-Finnish) · 42/1,180,010 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00279% 45/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,095
African / African-American	0.00267%	37,465
South Asian	0.0011%	91,084

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.Arg48Ser
Coding: c.142C>A
MANE Select: NM_004088
dbSNP: rs779136442
Type: single nucleotide variant
Location: chr10:96304639 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.49 · 2 PDB
Residue 48: the brct domain; an α-helix

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-arg48ser (accessed [today's date]).

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