Is CHAD p.Ala342Asp (c.1025C>A) pathogenic?

CHAD p.Ala342Asp (c.1025C>A) is classified Likely benign in CHAD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.754); Rare (popmax 0.569%, nfe).

How common is CHAD p.Ala342Asp (c.1025C>A) in the general population?

CHAD p.Ala342Asp (c.1025C>A) is rare (popmax 0.569%, nfe) (gnomAD).

What do computational predictors say about CHAD p.Ala342Asp (c.1025C>A)?

AlphaMissense predicts likely pathogenic (score 0.754) — an in-silico prediction, not a clinical call.

CHAD p.Ala342Asp

c.1025C>A · VCV3770411

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.754 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.569%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.754	likely pathogenic
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,512 bp · p 0.21 · regional, not allelic
Overall
CADD	25.1	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 0.569% European (non-Finnish) · 6,713/1,180,014 alleles

Filtering AF 0.557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.553%

Overall 0.482% 7,772/1,614,094 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.861%	116
European (non-Finnish)grpmax	0.569%	176
Remaining individualsnot grpmax-eligible	0.427%	234
Amishnot grpmax-eligible	0.329%	304
Middle Eastern	0.214%	466
Admixed American	0.112%	896
South Asian	0.0966%	1,035
African / African-American	0.0773%	1,293
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467

Finnish 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.Ala342Asp
Coding: c.1025C>A
MANE Select: NM_025149 · reported on NM_001267
Type: single nucleotide variant
Location: chr17:50465353 (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-ala342asp (accessed [today's date]).

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