Is KHK p.Asp154= (c.462C>T) pathogenic?

KHK p.Asp154= (c.462C>T) is classified Likely benign in KHK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-25). Very rare (popmax 0.00659%, sas); Associated with KHK-related disorder.

What condition is associated with KHK p.Asp154= (c.462C>T)?

KHK p.Asp154= (c.462C>T) is associated with KHK-related disorder (ClinVar).

How common is KHK p.Asp154= (c.462C>T) in the general population?

KHK p.Asp154= (c.462C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

KHK p.Asp154=

c.462C>T · VCV3352783

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

KHK-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 -4.2	GERP -4.7
Overall
CADD	0.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,086 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00124% 20/1,613,858 alleles · very rare exomes 19/1,461,658 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
Admixed American	0.005%	20,004
East Asian	0.00223%	44,900
Finnishnot grpmax-eligible	0.00157%	63,776
African / African-American	0.00133%	74,944
European (non-Finnish)	0.000678%	147,507

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: KHK
Protein: p.Asp154=
Coding: c.462C>T
MANE Select: NM_006488
Type: single nucleotide variant
Location: chr2:27097547 (GRCh38)
Gene constraint: LOEUF 1.362 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.32 · 38 PDB
Residue 154: an α-helix

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

Disease context

KHK-related disorder

Similar variants

KHK c.418-5A>G Likely benign same condition
KHK p.Thr48= Likely benign same condition
KHK p.Ala155Thr Uncertain significance ★★ ⚠ same type
KHK p.Asn157Thr Uncertain significance ★★ ⚠ same type
KHK p.Ser273Asn Uncertain significance ★★ ⚠ same type
KHK p.Thr158Asn Uncertain significance ★★ ⚠ same type
KHK c.210-328A>G Benign ★★ same type
KHK c.-245G>A Benign ★★ 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/khk-p-asp154 (accessed [today's date]).

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