Is HKDC1 p.Lys89Asn (c.267G>C) pathogenic?

HKDC1 p.Lys89Asn (c.267G>C) is classified Uncertain significance in HKDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2561); Absent from gnomAD v4.1.

How common is HKDC1 p.Lys89Asn (c.267G>C) in the general population?

HKDC1 p.Lys89Asn (c.267G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HKDC1 p.Lys89Asn (c.267G>C)?

AlphaMissense predicts likely benign (score 0.2561) — an in-silico prediction, not a clinical call.

HKDC1 p.Lys89Asn

c.267G>C · VCV4271158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2561 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2561	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -1.37	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 1	GERP -5.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 46 kb · p 0.93 · regional, not allelic
Overall
CADD	11.53	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: HKDC1
Protein: p.Lys89Asn
Coding: c.267G>C
MANE Select: NM_025130
Type: single nucleotide variant
Location: chr10:69232804 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37
Residue 89: the hexokinase 1 domain; a binding site; the 'hexokinase small subdomain 1' region

Full HKDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HKDC1 p.Thr58Met Likely pathogenic ★★ ⚠ same type
HKDC1 p.Phe528Ser Uncertain significance ★★ ⚠ same type
HKDC1 p.Val371Ile Uncertain significance ★★ ⚠ same type
HKDC1 p.Ala824= Benign ★★ same type
HKDC1 p.Thr66Ile Benign ★★ same type
HKDC1 c.1265+2T>C Likely pathogenic ★ same type
HKDC1 p.Asp84Asn Likely pathogenic ★ same type
HKDC1 p.Tyr417Cys Likely pathogenic ★ 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/hkdc1-p-lys89asn (accessed [today's date]).

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