Is CHSY1 p.Asn85Asp (c.253A>G) pathogenic?

CHSY1 p.Asn85Asp (c.253A>G) is classified Uncertain significance in CHSY1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-16). AlphaMissense: likely benign (0.0766); Very rare (popmax 0.00506%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHSY1 p.Asn85Asp (c.253A>G)?

CHSY1 p.Asn85Asp (c.253A>G) is associated with Inborn genetic diseases, temtamy preaxial brachydactyly syndrome (ClinVar).

How common is CHSY1 p.Asn85Asp (c.253A>G) in the general population?

CHSY1 p.Asn85Asp (c.253A>G) is very rare (popmax 0.00506%, amr) (gnomAD).

What do computational predictors say about CHSY1 p.Asn85Asp (c.253A>G)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

CHSY1 p.Asn85Asp

c.253A>G · rs762384442 · VCV1393761

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00506%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -3.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 16 kb · p 0.0015 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00506% Admixed American · 3/59,338 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.003% 48/1,598,146 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00506%	19,779
Remaining individualsnot grpmax-eligible	0.00484%	20,661
European (non-Finnish)	0.00357%	28,001

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.Asn85Asp
Coding: c.253A>G
MANE Select: NM_014918
dbSNP: rs762384442
Type: single nucleotide variant
Location: chr15:101251204 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: temtamy preaxial brachydactyly syndrome

Similar variants

CHSY1 p.Asn85= Benign/Likely benign ★★ same residue
CHSY1 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
CHSY1 p.Ala471Thr 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

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-asn85asp (accessed [today's date]).

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