Is HK2 p.Phe167= (c.501C>T) pathogenic?

HK2 p.Phe167= (c.501C>T) is classified Likely benign in HK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Rare (popmax 0.38%, mid); Associated with HK2-related disorder.

What condition is associated with HK2 p.Phe167= (c.501C>T)?

HK2 p.Phe167= (c.501C>T) is associated with HK2-related disorder (ClinVar).

How common is HK2 p.Phe167= (c.501C>T) in the general population?

HK2 p.Phe167= (c.501C>T) is rare (popmax 0.38%, mid) (gnomAD).

HK2 p.Phe167=

c.501C>T · rs138918973 · VCV3042674

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.38%, mid)

Conditions

HK2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.062, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.38% Middle Eastern · 23/6,060 alleles

Filtering AF 0.259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.0337% 543/1,612,806 alleles · rare exomes 487/1,460,492 · genomes 56/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.38%	263
Admixed American	0.06%	1,667
Remaining individualsnot grpmax-eligible	0.0544%	1,837
South Asian	0.0527%	1,897
European (non-Finnish)	0.0331%	3,023
Finnishnot grpmax-eligible	0.00937%	10,667
African / African-American	0.00533%	18,753
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
East Asian	0.00223%	44,880

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: HK2
Protein: p.Phe167=
Coding: c.501C>T
MANE Select: NM_000189
dbSNP: rs138918973
Type: single nucleotide variant
Location: chr2:74873281 (GRCh38)
Structure: AlphaFold pLDDT 82.81
Residue 167: the 'sufficient for interaction with microtubules' region

Full HK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HK2-related disorder

Similar variants

HOOK2 p.Tyr167Cys Uncertain significance ★ ⚠ same residue
HK2 c.591+10G>A Benign same condition
HK2 p.Ala113= Likely benign same condition
HK2 p.Ala387= Likely benign same condition
HK2 p.Ala387Ser Benign same condition
HK2 p.Ala424= Likely benign same condition
HK2 p.Ala831= Benign same condition
HK2 p.Arg844Lys Benign 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/hk2-p-phe167 (accessed [today's date]).

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