Is CHAD p.Arg163His (c.488G>A) pathogenic?

CHAD p.Arg163His (c.488G>A) is classified Uncertain significance in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1416); Rare (popmax 0.152%, afr).

How common is CHAD p.Arg163His (c.488G>A) in the general population?

CHAD p.Arg163His (c.488G>A) is rare (popmax 0.152%, afr) (gnomAD).

What do computational predictors say about CHAD p.Arg163His (c.488G>A)?

AlphaMissense predicts likely benign (score 0.1416) — an in-silico prediction, not a clinical call.

CHAD p.Arg163His

c.488G>A · rs376509429 · VCV2509568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1416 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.152%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1416	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -2.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.152% African / African-American · 114/75,066 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.00781% 126/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.152%	658
Admixed American	0.0117%	8,576
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00223%	44,884

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.Arg163His
Coding: c.488G>A
MANE Select: NM_025149 · reported on NM_001267
dbSNP: rs376509429
Type: single nucleotide variant
Location: chr17:50468326 (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-arg163his (accessed [today's date]).

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