Is CHN2 p.Arg39His (c.116G>A) pathogenic?

CHN2 p.Arg39His (c.116G>A) is classified Uncertain significance in CHN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: ambiguous (0.3553); Very rare (popmax 0.00553%, sas).

How common is CHN2 p.Arg39His (c.116G>A) in the general population?

CHN2 p.Arg39His (c.116G>A) is very rare (popmax 0.00553%, sas) (gnomAD).

What do computational predictors say about CHN2 p.Arg39His (c.116G>A)?

AlphaMissense predicts ambiguous (score 0.3553) — an in-silico prediction, not a clinical call.

CHN2 p.Arg39His

c.116G>A · VCV4002474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3553	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -7.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 318 kb · p 0.0002 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.00553% South Asian · 5/90,452 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00329% 53/1,610,384 alleles · very rare exomes 46/1,458,398 · genomes 7/151,986 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00553%	18,090
African / African-American	0.00535%	18,694
European (non-Finnish)	0.00365%	27,405
East Asian	0.00224%	44,652

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.Arg39His
Coding: c.116G>A
MANE Select: NM_004067
Type: single nucleotide variant
Location: chr7:29367959 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB

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

Similar variants

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.Arg404Trp Uncertain significance ★ ⚠ same type
CHN2 p.Arg47Gln Uncertain significance ★ ⚠ same type
CHN2 p.Arg87Gln 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-arg39his (accessed [today's date]).

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