Is CHIT1 p.Ser339Arg (c.1017C>G) pathogenic?

CHIT1 p.Ser339Arg (c.1017C>G) is classified Uncertain significance in CHIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely pathogenic (0.9854); Absent from gnomAD v4.1.

How common is CHIT1 p.Ser339Arg (c.1017C>G) in the general population?

CHIT1 p.Ser339Arg (c.1017C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHIT1 p.Ser339Arg (c.1017C>G)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

CHIT1 p.Ser339Arg

c.1017C>G · VCV3492291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic · top 1% in CHIT1
REVEL	0.471	indeterminate
SaProt	LLR -16.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.4, 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

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

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.Ser339Arg
Coding: c.1017C>G
MANE Select: NM_003465
Type: single nucleotide variant
Location: chr1:203219228 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 23 PDB
Residue 339: the gh18 domain; an α-helix

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-ser339arg (accessed [today's date]).

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