Is CHN1 p.Leu184= (c.550T>C) pathogenic?

CHN1 p.Leu184= (c.550T>C) is classified Likely benign in CHN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). Very rare (popmax 0.000349%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHN1 p.Leu184= (c.550T>C)?

CHN1 p.Leu184= (c.550T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHN1 p.Leu184= (c.550T>C) in the general population?

CHN1 p.Leu184= (c.550T>C) is very rare (popmax 0.000349%, nfe) (gnomAD).

CHN1 p.Leu184=

c.550T>C · VCV4228247

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Conditions

Inborn genetic diseases

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 7	GERP -0.21, phastCons 1
Overall
CADD	14.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000349% European (non-Finnish) · 4/1,147,762 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000257% 4/1,553,630 alleles · very rare

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: CHN1
Protein: p.Leu184=
Coding: c.550T>C
MANE Select: NM_001822
Type: single nucleotide variant
Location: chr2:174846957 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 2 PDB

Full CHN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHN1 p.Ala27Gly Uncertain significance ★★ ⚠ same condition
CHN1 p.Asp440Gly Uncertain significance ★★ ⚠ same condition
CHN1 p.Arg295Ile Uncertain significance ★ same condition
CHN1 p.Arg321Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
CHN1 p.Arg428Lys Uncertain significance ★ ⚠ same condition
CHN1 p.Arg73Trp Uncertain significance ★ ⚠ same condition
CHN1 p.Asn207Ser Uncertain significance ★ ⚠ same condition
CHN1 p.Asn337Thr Uncertain significance ★ ⚠ same condition

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/chn1-p-leu184 (accessed [today's date]).

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