Is CHIT1 p.Ser288Phe (c.863C>T) pathogenic?

CHIT1 p.Ser288Phe (c.863C>T) is classified Uncertain significance in CHIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1189); Absent from gnomAD v4.1.

How common is CHIT1 p.Ser288Phe (c.863C>T) in the general population?

CHIT1 p.Ser288Phe (c.863C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHIT1 p.Ser288Phe (c.863C>T)?

AlphaMissense predicts likely benign (score 0.1189) — an in-silico prediction, not a clinical call.

CHIT1 p.Ser288Phe

c.863C>T · VCV4228136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1189 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1189	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.95 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 0.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.56 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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: CHIT1
Protein: p.Ser288Phe
Coding: c.863C>T
MANE Select: NM_003465
Type: single nucleotide variant
Location: chr1:203219716 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 23 PDB
Residue 288: the gh18 domain; a β-strand

Full CHIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHIT1 c.-13G>A Uncertain significance ★★ same type
CHIT1 c.*119C>T Uncertain significance ★★ same type
CHIT1 p.Arg128His Uncertain significance ★★ ⚠ same type
CHIT1 p.Arg432Trp Uncertain significance ★★ ⚠ same type
CHIT1 p.Pro451Arg Uncertain significance ★★ ⚠ same type
CHIT1 c.25+8G>T Likely benign ★★ same type
CHIT1 c.258-6T>C Benign ★★ same type
CHIT1 p.Ala442Gly Benign ★★ 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/chit1-p-ser288phe (accessed [today's date]).

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