Is CHSY1 p.Gln491= (c.1473A>G) pathogenic?

CHSY1 p.Gln491= (c.1473A>G) is classified Benign in CHSY1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). Common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Gln491= (c.1473A>G)?

CHSY1 p.Gln491= (c.1473A>G) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

CHSY1 p.Gln491=

Q: How common is CHSY1 p.Gln491= (c.1473A>G) in the general population?

CHSY1 p.Gln491= (c.1473A>G) is common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1473A>G · rs76457230 · VCV466169

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 9.4%, eas) — 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 -0.85	GERP -3.5
Overall
CADD	0.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.4% East Asian · 4,204/44,700 alleles

Filtering AF 9.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.07%

Overall 1.86% 29,848/1,608,234 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.4%	11
Admixed American	5.24%	19
African / African-American	4.02%	25
Ashkenazi Jewishnot grpmax-eligible	3.02%	33
Finnishnot grpmax-eligible	2.72%	37
Remaining individualsnot grpmax-eligible	2.49%	40
Middle Eastern	1.54%	65
South Asian	1.4%	71
European (non-Finnish)	1.19%	84
Amishnot grpmax-eligible	0.329%	304

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.Gln491=
Coding: c.1473A>G
MANE Select: NM_014918
dbSNP: rs76457230
Type: single nucleotide variant
Location: chr15:101178324 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.20

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.Gln491Arg Uncertain significance ★ ⚠ same residue
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

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-gln491 (accessed [today's date]).

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