Is CHSY1 p.Arg40= (c.120G>C) pathogenic?

CHSY1 p.Arg40= (c.120G>C) is classified Likely benign in CHSY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). Ultra-rare (popmax 0.0204%, nfe); Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Arg40= (c.120G>C)?

CHSY1 p.Arg40= (c.120G>C) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

How common is CHSY1 p.Arg40= (c.120G>C) in the general population?

CHSY1 p.Arg40= (c.120G>C) is ultra-rare (popmax 0.0204%, nfe) (gnomAD).

CHSY1 p.Arg40=

c.120G>C · rs772693719 · VCV2055051

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, nfe)

Conditions

temtamy preaxial brachydactyly syndrome

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 3.2	GERP 1.1, phastCons 1
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% European (non-Finnish) · 187/914,534 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.017% 194/1,138,288 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0204%	4,891
Remaining individualsnot grpmax-eligible	0.0138%	7,268
Finnishnot grpmax-eligible	0.00565%	17,690
African / African-American	0.00167%	59,752

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: CHSY1
Protein: p.Arg40=
Coding: c.120G>C
MANE Select: NM_014918
dbSNP: rs772693719
Type: single nucleotide variant
Location: chr15:101251337 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.20
Residue 40: the 'disordered' region

Full CHSY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

temtamy preaxial brachydactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHSY1 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
CHSY1 p.Ala61Val Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg180His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg229Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg233Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg244Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg322His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg336Cys 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/chsy1-p-arg40 (accessed [today's date]).

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