Is CHSY1 p.Val91Phe (c.271G>T) pathogenic?

CHSY1 p.Val91Phe (c.271G>T) is classified Uncertain significance in CHSY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.942); No allele count reported in gnomAD v4.1 (AN 1,600,986); Associated with Inborn genetic diseases.

What condition is associated with CHSY1 p.Val91Phe (c.271G>T)?

CHSY1 p.Val91Phe (c.271G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHSY1 p.Val91Phe (c.271G>T) in the general population?

CHSY1 p.Val91Phe (c.271G>T) is no allele count reported in gnomAD v4.1 (AN 1,600,986) (gnomAD).

What do computational predictors say about CHSY1 p.Val91Phe (c.271G>T)?

AlphaMissense predicts likely pathogenic (score 0.942) — an in-silico prediction, not a clinical call.

CHSY1 p.Val91Phe

c.271G>T · rs2039106599 · VCV2339755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.942 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,986)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.942	likely pathogenic
REVEL	0.542	indeterminate
SaProt	LLR -16.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 16 kb · p 0.0015 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,600,986). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHSY1
Protein: p.Val91Phe
Coding: c.271G>T
MANE Select: NM_014918
dbSNP: rs2039106599
Type: single nucleotide variant
Location: chr15:101251186 (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

Similar variants

CHSY1 p.Ala471Thr Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg180His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg229Trp Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg322His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg336Cys Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg368His Uncertain significance ★★ ⚠ same condition
CHSY1 p.Arg423Gly Uncertain significance ★★ ⚠ same condition
CHSY1 p.Asn85Asp 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-val91phe (accessed [today's date]).

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