Is HCK p.Asn64= (c.192T>C) pathogenic?

HCK p.Asn64= (c.192T>C) is classified Benign in HCK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). Low-frequency (popmax 1.59%, mid).

How common is HCK p.Asn64= (c.192T>C) in the general population?

HCK p.Asn64= (c.192T>C) is low-frequency (popmax 1.59%, mid) (gnomAD).

HCK p.Asn64=

c.192T>C · rs34513177 · VCV3239003

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, mid)

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 -0.25	GERP -1.8
Overall
CADD	1.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.59% Middle Eastern · 96/6,056 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.27%

Overall 0.837% 13,489/1,611,380 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	7.13%	14
Ashkenazi Jewishnot grpmax-eligible	1.98%	50
Middle Easterngrpmax	1.59%	63
Finnishnot grpmax-eligible	1.42%	71
African / African-American	1.36%	73
Remaining individualsnot grpmax-eligible	1.08%	92
Admixed American	0.882%	113
European (non-Finnish)	0.79%	127
South Asian	0.334%	299
East Asian	0.00223%	44,822

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: HCK
Protein: p.Asn64=
Coding: c.192T>C
MANE Select: NM_002110
dbSNP: rs34513177
Type: single nucleotide variant
Location: chr20:32073327 (GRCh38)
Gene constraint: LOEUF 0.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.93 · 42 PDB

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

Similar variants

HCK p.Arg123Trp Uncertain significance ★★ ⚠ same type
HCK p.Glu75Gln Uncertain significance ★★ ⚠ same type
HCK p.Leu139Val Uncertain significance ★★ ⚠ same type
HCK p.Ser5Pro Uncertain significance ★★ ⚠ same type
HCK p.Ala44Thr Benign/Likely benign ★★ same type
HCK p.Asp231= Benign/Likely benign ★★ same type
HCK p.Glu110= Likely benign ★★ same type
HCK p.Pro49Ala Likely 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/hck-p-asn64 (accessed [today's date]).

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