Is CHST5 p.Arg349Leu (c.1046G>T) pathogenic?

CHST5 p.Arg349Leu (c.1046G>T) is classified Likely benign in CHST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). AlphaMissense: likely benign (0.0741); Ultra-rare (popmax 0.0174%, nfe).

How common is CHST5 p.Arg349Leu (c.1046G>T) in the general population?

CHST5 p.Arg349Leu (c.1046G>T) is ultra-rare (popmax 0.0174%, nfe) (gnomAD).

What do computational predictors say about CHST5 p.Arg349Leu (c.1046G>T)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

CHST5 p.Arg349Leu

c.1046G>T · rs141860770 · VCV2357256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.02	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 0.9	GERP -3.5, phastCons 0.98
Regional constraint	o/e 1.06	unconstrained · MANE · 1,232 bp · p 0.16 · regional, not allelic
Overall
CADD	0.589	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

Grpmax group 0.0174% European (non-Finnish) · 205/1,179,860 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0133% 215/1,613,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0174%	5,755
Remaining individualsnot grpmax-eligible	0.008%	12,494
African / African-American	0.00534%	18,733
Admixed American	0.00167%	60,002

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: CHST5
Protein: p.Arg349Leu
Coding: c.1046G>T
MANE Select: NM_024533
dbSNP: rs141860770
Type: single nucleotide variant
Location: chr16:75529339 (GRCh38)
Gene constraint: LOEUF 1.549 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 88.60

Full CHST5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST5 p.Ala311Thr Benign ★★ same type
CHST5 p.Arg6Trp Benign ★★ ⚠ same type
CHST5 p.Glu322Gln Benign ★★ same type
CHST5 p.Ala11Val Uncertain significance ★ ⚠ same type
CHST5 p.Ala150Glu Uncertain significance ★ ⚠ same type
CHST5 p.Ala159Thr Uncertain significance ★ ⚠ same type
CHST5 p.Ala214Thr Uncertain significance ★ ⚠ same type
CHST5 p.Ala275Ser 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/chst5-p-arg349leu (accessed [today's date]).

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