Is CHSY1 p.Arg101= (c.303G>C) pathogenic?

CHSY1 p.Arg101= (c.303G>C) is classified Benign in CHSY1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 45.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Arg101= (c.303G>C)?

CHSY1 p.Arg101= (c.303G>C) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

CHSY1 p.Arg101=

Q: How common is CHSY1 p.Arg101= (c.303G>C) in the general population?

CHSY1 p.Arg101= (c.303G>C) is common (popmax 45.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.303G>C · rs7176149 · VCV585674

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 45.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.7, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.6% African / African-American · 33,914/74,294 alleles

Filtering AF 45.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.1%

Overall 16.1% 256,497/1,589,722 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	45.6%	2
Middle Eastern	23.4%	4
Amishnot grpmax-eligible	21.7%	5
Admixed American	18.4%	5
Remaining individualsnot grpmax-eligible	17.5%	6
South Asian	15.2%	7
European (non-Finnish)	14.8%	7
Ashkenazi Jewishnot grpmax-eligible	13.7%	7
Finnishnot grpmax-eligible	9.8%	10
East Asian	7.17%	14

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.Arg101=
Coding: c.303G>C
MANE Select: NM_014918
dbSNP: rs7176149
Type: single nucleotide variant
Location: chr15:101251154 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.20
Residue 101: a binding site

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-arg101 (accessed [today's date]).

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