Is CHSY1 p.Val604= (c.1812G>A) pathogenic?

CHSY1 p.Val604= (c.1812G>A) is classified Benign in CHSY1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). Common (popmax 5.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Val604= (c.1812G>A)?

CHSY1 p.Val604= (c.1812G>A) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

CHSY1 p.Val604=

Q: How common is CHSY1 p.Val604= (c.1812G>A) in the general population?

CHSY1 p.Val604= (c.1812G>A) is common (popmax 5.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1812G>A · rs3803422 · VCV466170

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.8%, 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 3.5	GERP 0.93, phastCons 1
Overall
CADD	9.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.8% East Asian · 2,602/44,880 alleles

Filtering AF 5.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.54%

Overall 1.54% 24,786/1,614,176 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.8%	17
Admixed American	4.93%	20
Ashkenazi Jewishnot grpmax-eligible	3.02%	33
Finnishnot grpmax-eligible	2.72%	37
Remaining individualsnot grpmax-eligible	1.82%	55
South Asian	1.26%	79
European (non-Finnish)	1.17%	85
Middle Eastern	1.11%	90
African / African-American	0.506%	197
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.Val604=
Coding: c.1812G>A
MANE Select: NM_014918
dbSNP: rs3803422
Type: single nucleotide variant
Location: chr15:101177985 (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.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-val604 (accessed [today's date]).

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