Is DTNB p.Ala613Ser (c.1837G>T) pathogenic?

DTNB p.Ala613Ser (c.1837G>T) is classified Uncertain significance in DTNB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.0731); Very rare (popmax 8.48e-05%, nfe).

How common is DTNB p.Ala613Ser (c.1837G>T) in the general population?

DTNB p.Ala613Ser (c.1837G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DTNB p.Ala613Ser (c.1837G>T)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

DTNB p.Ala613Ser

c.1837G>T · rs2038657271 · VCV2327675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.04	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 0.46	GERP -1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 273 kb · p 0.026 · regional, not allelic
Overall
CADD	15.29	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 8.48e-05% European (non-Finnish) · 1/1,179,890 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very 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: DTNB
Protein: p.Ala613Ser
Coding: c.1837G>T
MANE Select: NM_021907
dbSNP: rs2038657271
Type: single nucleotide variant
Location: chr2:25383878 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.29
Residue 613: the 'disordered' region

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

Similar variants

DTNB p.Val568= Benign ★★ same type
DTNB p.Ala134Thr Uncertain significance ★ ⚠ same type
DTNB p.Ala376Val Uncertain significance ★ ⚠ same type
DTNB p.Ala410Ser Uncertain significance ★ ⚠ same type
DTNB p.Ala526Thr Uncertain significance ★ ⚠ same type
DTNB p.Ala575Val Uncertain significance ★ ⚠ same type
DTNB p.Ala577Thr Uncertain significance ★ ⚠ same type
DTNB p.Ala61Gly 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/dtnb-p-ala613ser (accessed [today's date]).

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