Is CHAD p.Arg344Cys (c.1030C>T) pathogenic?

CHAD p.Arg344Cys (c.1030C>T) is classified Uncertain significance in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely pathogenic (0.6024); Very rare (popmax 0.00533%, afr).

How common is CHAD p.Arg344Cys (c.1030C>T) in the general population?

CHAD p.Arg344Cys (c.1030C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about CHAD p.Arg344Cys (c.1030C>T)?

AlphaMissense predicts likely pathogenic (score 0.6024) — an in-silico prediction, not a clinical call.

CHAD p.Arg344Cys

c.1030C>T · rs202147669 · VCV2463519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6024 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6024	likely pathogenic
REVEL	0.17	moderately benign-leaning
SaProt	LLR -12.29	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	27.6	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 0.00533% African / African-American · 4/75,018 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00545% 88/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Remaining individualsnot grpmax-eligible	0.0144%	6,945
African / African-Americangrpmax	0.00533%	18,755
East Asian	0.00446%	22,427
South Asian	0.00329%	30,353
European (non-Finnish)	0.00288%	34,707

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg344Cys
Coding: c.1030C>T
MANE Select: NM_025149 · reported on NM_001267
dbSNP: rs202147669
Type: single nucleotide variant
Location: chr17:50465348 (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-arg344cys (accessed [today's date]).

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