Is HUNK p.Lys96Arg (c.287A>G) pathogenic?

HUNK p.Lys96Arg (c.287A>G) is classified Uncertain significance in HUNK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.1228); Very rare (popmax 0.00933%, afr).

How common is HUNK p.Lys96Arg (c.287A>G) in the general population?

HUNK p.Lys96Arg (c.287A>G) is very rare (popmax 0.00933%, afr) (gnomAD).

What do computational predictors say about HUNK p.Lys96Arg (c.287A>G)?

AlphaMissense predicts likely benign (score 0.1228) — an in-silico prediction, not a clinical call.

HUNK p.Lys96Arg

c.287A>G · rs138361949 · VCV3107630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1228	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 101 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	19.91	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

Grpmax group 0.00933% African / African-American · 7/75,000 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000558% 9/1,614,032 alleles · very rare exomes 4/1,461,724 · genomes 5/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,714
Admixed American	0.00333%	29,996

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: HUNK
Protein: p.Lys96Arg
Coding: c.287A>G
MANE Select: NM_014586
dbSNP: rs138361949
Type: single nucleotide variant
Location: chr21:31924493 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.83
Residue 96: the protein kinase domain

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

Similar variants

HUNK p.Ala272Ser Uncertain significance ★ ⚠ same type
HUNK p.Ala4Val Uncertain significance ★ ⚠ same type
HUNK p.Ala590Asp Uncertain significance ★ ⚠ same type
HUNK p.Ala698Gly Uncertain significance ★ ⚠ same type
HUNK p.Arg119His Uncertain significance ★ ⚠ same type
HUNK p.Arg157Trp Uncertain significance ★ same type
HUNK p.Arg164His Uncertain significance ★ ⚠ same type
HUNK p.Arg179Trp Uncertain significance ★ 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/hunk-p-lys96arg (accessed [today's date]).

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