Is CHN2 p.Arg87Trp (c.259C>T) pathogenic?

CHN2 p.Arg87Trp (c.259C>T) is classified Uncertain significance in CHN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely pathogenic (0.9578); Very rare (popmax 0.0022%, sas).

How common is CHN2 p.Arg87Trp (c.259C>T) in the general population?

CHN2 p.Arg87Trp (c.259C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CHN2 p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely pathogenic (score 0.9578) — an in-silico prediction, not a clinical call.

CHN2 p.Arg87Trp

c.259C>T · rs950872576 · VCV2307556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9578	likely pathogenic
REVEL	0.634	indeterminate
SaProt	LLR -16.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.68, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 318 kb · p 0.0002 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,062 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000372% 6/1,612,886 alleles · very rare exomes 5/1,460,724 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00316%	31,669
South Asiangrpmax	0.0022%	45,531
European (non-Finnish)	0.00017%	589,817

Finnish 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: CHN2
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_004067
dbSNP: rs950872576
Type: single nucleotide variant
Location: chr7:29398455 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 87: the sh2 domain; a β-strand

Full CHN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHN2 p.Arg87Gln Uncertain significance ★ ⚠ same residue
CHN2 p.Ala201Val Uncertain significance ★ ⚠ same type
CHN2 p.Ala3Thr Uncertain significance ★ ⚠ same type
CHN2 p.Arg290Ser Uncertain significance ★ ⚠ same type
CHN2 p.Arg299Gln Uncertain significance ★ ⚠ same type
CHN2 p.Arg313Thr Uncertain significance ★ ⚠ same type
CHN2 p.Arg39His Uncertain significance ★ ⚠ same type
CHN2 p.Arg404Trp 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/chn2-p-arg87trp (accessed [today's date]).

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