Is CHSY1 p.Val635= (c.1905G>C) pathogenic?

CHSY1 p.Val635= (c.1905G>C) is classified Benign in CHSY1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 40.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with temtamy preaxial brachydactyly syndrome.

What condition is associated with CHSY1 p.Val635= (c.1905G>C)?

CHSY1 p.Val635= (c.1905G>C) is associated with temtamy preaxial brachydactyly syndrome (ClinVar).

CHSY1 p.Val635=

Q: How common is CHSY1 p.Val635= (c.1905G>C) in the general population?

CHSY1 p.Val635= (c.1905G>C) is common (popmax 40.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1905G>C · rs28364839 · VCV672147

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 40.9%, 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 -0.81	GERP 0.93, phastCons 0.003
Overall
CADD	1.901	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.9% African / African-American · 30,637/74,932 alleles

Filtering AF 40.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 40.3%

Overall 23% 371,789/1,613,890 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	40.9%	2
Middle Eastern	33%	3
Ashkenazi Jewishnot grpmax-eligible	27%	4
South Asian	24.3%	4
Remaining individualsnot grpmax-eligible	23.8%	4
Amishnot grpmax-eligible	23.1%	4
European (non-Finnish)	22.7%	4
Finnishnot grpmax-eligible	21.5%	5
Admixed American	16.9%	6
East Asian	4.68%	21

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.Val635=
Coding: c.1905G>C
MANE Select: NM_014918
dbSNP: rs28364839
Type: single nucleotide variant
Location: chr15:101177892 (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-val635 (accessed [today's date]).

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