Is CHAD p.Ala73Asp (c.218C>A) pathogenic?

CHAD p.Ala73Asp (c.218C>A) is classified Uncertain significance in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: likely benign (0.0979); Ultra-rare (popmax 0.02%, eas).

How common is CHAD p.Ala73Asp (c.218C>A) in the general population?

CHAD p.Ala73Asp (c.218C>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about CHAD p.Ala73Asp (c.218C>A)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

CHAD p.Ala73Asp

c.218C>A · rs748324358 · VCV2533199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -1.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP -2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	17.62	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 0.02% East Asian · 9/44,892 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00105% 17/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
African / African-American	0.00934%	10,708
South Asian	0.0011%	91,092

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.Ala73Asp
Coding: c.218C>A
MANE Select: NM_025149 · reported on NM_001267
dbSNP: rs748324358
Type: single nucleotide variant
Location: chr17:50468596 (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-ala73asp (accessed [today's date]).

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