Is CHN1 p.Pro79= (c.237A>G) pathogenic?

CHN1 p.Pro79= (c.237A>G) is classified Conflicting classifications of pathogenicity in CHN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-10-10). Ultra-rare (popmax 0.0537%, nfe); Associated with Duane retraction syndrome 2.

What condition is associated with CHN1 p.Pro79= (c.237A>G)?

CHN1 p.Pro79= (c.237A>G) is associated with Duane retraction syndrome 2 (ClinVar).

How common is CHN1 p.Pro79= (c.237A>G) in the general population?

CHN1 p.Pro79= (c.237A>G) is ultra-rare (popmax 0.0537%, nfe) (gnomAD).

CHN1 p.Pro79=

c.237A>G · rs377261893 · VCV725227

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0537%, nfe)

Conditions

Duane retraction syndrome 2

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 -1.3	GERP -4, phastCons 0.001
Overall
CADD	4.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0537% European (non-Finnish) · 633/1,178,904 alleles

Filtering AF 0.0502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.0423% 681/1,611,468 alleles · ultra-rare exomes 624/1,459,350 · genomes 57/152,118 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0537%	1,862
Remaining individualsnot grpmax-eligible	0.0449%	2,229
Middle Eastern	0.0331%	3,023
Admixed American	0.0167%	5,982
African / African-American	0.0107%	9,366

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.Pro79=
Coding: c.237A>G
MANE Select: NM_001822
dbSNP: rs377261893
Type: single nucleotide variant
Location: chr2:174915081 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 2 PDB
Residue 79: the sh2 domain

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

Disease context

Duane retraction syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHN1 c.-160C>G Uncertain significance ★★ same condition
CHN1 c.-74C>T Uncertain significance ★★ same condition
CHN1 p.Ala27Gly Uncertain significance ★★ ⚠ same condition
CHN1 p.Asp440Gly Uncertain significance ★★ ⚠ same condition
CHN1 p.Lys260Asn Uncertain significance ★★ ⚠ same condition
CHN1 p.Thr167Ile Uncertain significance ★★ ⚠ same condition
CHN1 p.Val65Met Uncertain significance ★★ ⚠ same condition
CHN1 c.886+15G>A Benign ★★ 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-pro79 (accessed [today's date]).

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