Is HUNK p.Pro242Arg (c.725C>G) pathogenic?

HUNK p.Pro242Arg (c.725C>G) is classified Uncertain significance in HUNK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.8151); Absent from gnomAD v4.1.

How common is HUNK p.Pro242Arg (c.725C>G) in the general population?

HUNK p.Pro242Arg (c.725C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HUNK p.Pro242Arg (c.725C>G)?

AlphaMissense predicts likely pathogenic (score 0.8151) — an in-silico prediction, not a clinical call.

HUNK p.Pro242Arg

c.725C>G · rs2516680827 · VCV2334526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8151 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8151	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 0.93, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 101 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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: HUNK
Protein: p.Pro242Arg
Coding: c.725C>G
MANE Select: NM_014586
dbSNP: rs2516680827
Type: single nucleotide variant
Location: chr21:31946150 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.83
Residue 242: 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-pro242arg (accessed [today's date]).

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