Is CHAD p.Ser291Arg (c.873C>G) pathogenic?

CHAD p.Ser291Arg (c.873C>G) is classified Uncertain significance in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.2188); Very rare (popmax 0.000678%, nfe).

How common is CHAD p.Ser291Arg (c.873C>G) in the general population?

CHAD p.Ser291Arg (c.873C>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CHAD p.Ser291Arg (c.873C>G)?

AlphaMissense predicts likely benign (score 0.2188) — an in-silico prediction, not a clinical call.

CHAD p.Ser291Arg

c.873C>G · VCV4001998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2188	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.4	GERP 0.34, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	22.5	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 0.000678% European (non-Finnish) · 8/1,179,998 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,892 alleles · very rare

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: CHAD
Protein: p.Ser291Arg
Coding: c.873C>G
MANE Select: NM_025149 · reported on NM_001267
Type: single nucleotide variant
Location: chr17:50465772 (GRCh38)

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

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/chad-p-ser291arg (accessed [today's date]).

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