Is DHTKD1 p.Ala210Thr (c.628G>A) pathogenic?

DHTKD1 p.Ala210Thr (c.628G>A) is classified Uncertain significance in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). AlphaMissense: likely benign (0.0937); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DHTKD1 p.Ala210Thr (c.628G>A)?

DHTKD1 p.Ala210Thr (c.628G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DHTKD1 p.Ala210Thr (c.628G>A) in the general population?

DHTKD1 p.Ala210Thr (c.628G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHTKD1 p.Ala210Thr (c.628G>A)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

DHTKD1 p.Ala210Thr

c.628G>A · VCV3271840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -7.54	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 9.7	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 52 kb · p 0.072 · regional, not allelic
Overall
CADD	23.5	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

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: DHTKD1
Protein: p.Ala210Thr
Coding: c.628G>A
MANE Select: NM_018706
Type: single nucleotide variant
Location: chr10:12087640 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 210: an α-helix

Full DHTKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHTKD1 p.Ala210Ser Benign/Likely benign ★★ same residue
DHTKD1 p.Trp861Ter Pathogenic ★★ same condition
DHTKD1 c.1159+5G>A Uncertain significance ★★ same condition
DHTKD1 p.Ala113Pro Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala275Val Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala297Val Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala723Val Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala81Thr Uncertain significance ★★ ⚠ same condition

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/dhtkd1-p-ala210thr (accessed [today's date]).

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