Is CHSY3 p.Phe607Leu (c.1821T>A) pathogenic?

CHSY3 p.Phe607Leu (c.1821T>A) is classified Uncertain significance in CHSY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.2851); Absent from gnomAD v4.1.

How common is CHSY3 p.Phe607Leu (c.1821T>A) in the general population?

CHSY3 p.Phe607Leu (c.1821T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHSY3 p.Phe607Leu (c.1821T>A)?

AlphaMissense predicts likely benign (score 0.2851) — an in-silico prediction, not a clinical call.

CHSY3 p.Phe607Leu

c.1821T>A · VCV4002835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2851	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -4, phastCons 0.06
Regional constraint	o/e 1.01	unconstrained · MANE · 985 bp · p 0.77 · regional, not allelic
Overall
CADD	12.98	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHSY3
Protein: p.Phe607Leu
Coding: c.1821T>A
MANE Select: NM_175856
Type: single nucleotide variant
Location: chr5:130184963 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97 · 2 PDB

Full CHSY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHSY3 p.Ala141Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Ala164Asp Uncertain significance ★ same type
CHSY3 p.Ala225Gly Uncertain significance ★ ⚠ same type
CHSY3 p.Ala53Val Uncertain significance ★ ⚠ same type
CHSY3 p.Ala793Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Ala859Thr Uncertain significance ★ ⚠ same type
CHSY3 p.Arg112Gln Uncertain significance ★ ⚠ same type
CHSY3 p.Arg145Trp Uncertain significance ★ ⚠ same type

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/chsy3-p-phe607leu (accessed [today's date]).

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