Is BCKDHA p.Phe324= (c.972C>T) pathogenic?

BCKDHA p.Phe324= (c.972C>T) is classified Benign in BCKDHA (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 82.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with maple syrup urine disease.

What condition is associated with BCKDHA p.Phe324= (c.972C>T)?

BCKDHA p.Phe324= (c.972C>T) is associated with maple syrup urine disease, maple syrup urine disease type 1A (ClinVar).

How is Maple syrup urine disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BCKDHA p.Phe324=

Q: How common is BCKDHA p.Phe324= (c.972C>T) in the general population?

BCKDHA p.Phe324= (c.972C>T) is common (popmax 82.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.972C>T · rs284652 · VCV93382

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 82.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Overall
CADD	14.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 82.5% African / African-American · 61,842/74,922 alleles

Filtering AF 82% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.8%

Overall 61.1% 985,066/1,613,360 alleles · common exomes 885,320/1,461,412 · genomes 99,746/151,948 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	82.5%	1
Amishnot grpmax-eligible	77%	1
Finnishnot grpmax-eligible	65.6%	2
Middle Eastern	63.5%	2
Ashkenazi Jewishnot grpmax-eligible	62.5%	2
Remaining individualsnot grpmax-eligible	61.5%	2
European (non-Finnish)	60.7%	2
South Asian	58.2%	2
Admixed American	50.4%	2
East Asian	45.6%	2

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: BCKDHA
Protein: p.Phe324=
Coding: c.972C>T
MANE Select: NM_000709
dbSNP: rs284652
Type: single nucleotide variant
Location: chr19:41422747 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.82 · 24 PDB
Residue 324: a β-strand

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

Disease context

maple syrup urine disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maple syrup urine disease type 1A

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

BCKDHA c.109-1G>A Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.1168-1G>A Likely pathogenic ★★ same condition
BCKDHA c.1168-2A>G Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.288+1G>A Pathogenic ★★ same condition
BCKDHA c.288+9C>T Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.376-2A>G Likely pathogenic ★★ same condition
BCKDHA c.647-1G>C Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.853+2T>C Likely pathogenic ★★ same condition

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/bckdha-p-phe324 (accessed [today's date]).

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