Is CHAD p.Thr350Ile (c.1049C>T) pathogenic?

CHAD p.Thr350Ile (c.1049C>T) is classified Benign in CHAD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-15). AlphaMissense: likely benign (0.148); Common (popmax 8.12%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CHAD p.Thr350Ile (c.1049C>T)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

CHAD p.Thr350Ile

Q: How common is CHAD p.Thr350Ile (c.1049C>T) in the general population?

CHAD p.Thr350Ile (c.1049C>T) is common (popmax 8.12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1049C>T · rs2231510 · VCV779024

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.12%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
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	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 8.12% African / African-American · 6,085/74,980 alleles

Filtering AF 7.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.88%

Overall 0.433% 6,995/1,614,038 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.12%	12
Remaining individualsnot grpmax-eligible	0.645%	155
Admixed American	0.528%	189
Middle Eastern	0.412%	242
South Asian	0.022%	4,553
European (non-Finnish)	0.0123%	8,138

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.Thr350Ile
Coding: c.1049C>T
MANE Select: NM_025149 · reported on NM_001267
dbSNP: rs2231510
Type: single nucleotide variant
Location: chr17:50465329 (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-thr350ile (accessed [today's date]).

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