Is CHDH p.Thr532Lys (c.1595C>A) pathogenic?

CHDH p.Thr532Lys (c.1595C>A) is classified Uncertain significance in CHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.8464); Very rare (popmax 0.00136%, nfe).

How common is CHDH p.Thr532Lys (c.1595C>A) in the general population?

CHDH p.Thr532Lys (c.1595C>A) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about CHDH p.Thr532Lys (c.1595C>A)?

AlphaMissense predicts likely pathogenic (score 0.8464) — an in-silico prediction, not a clinical call.

CHDH p.Thr532Lys

c.1595C>A · VCV3266929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8464 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8464	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,228 bp · p 0.86 · regional, not allelic
Overall
CADD	27.7	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 0.00136% European (non-Finnish) · 16/1,180,042 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00109% 16/1,461,848 alleles · very rare

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: CHDH
Protein: p.Thr532Lys
Coding: c.1595C>A
MANE Select: NM_018397
Type: single nucleotide variant
Location: chr3:53817967 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.84

Full CHDH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHDH p.Pro396Leu Uncertain significance ★★ ⚠ same type
CHDH c.704-3C>T Benign ★★ same type
CHDH p.Gly235= Benign ★★ same type
CHDH p.Val45= Benign ★★ same type
CHDH p.Ala13Val Uncertain significance ★ ⚠ same type
CHDH p.Ala170Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala177Thr Uncertain significance ★ ⚠ same type
CHDH p.Ala240Val Uncertain significance ★ ⚠ same type

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/chdh-p-thr532lys (accessed [today's date]).

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