Is ABCD4 p.Gln177Ter (c.529C>T) pathogenic?

ABCD4 p.Gln177Ter (c.529C>T) is classified Pathogenic in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). Absent from gnomAD v4.1; Associated with methylmalonic aciduria and homocystinuria type cblC.

What condition is associated with ABCD4 p.Gln177Ter (c.529C>T)?

ABCD4 p.Gln177Ter (c.529C>T) is associated with methylmalonic aciduria and homocystinuria type cblC (ClinVar).

How common is ABCD4 p.Gln177Ter (c.529C>T) in the general population?

ABCD4 p.Gln177Ter (c.529C>T) is absent from gnomAD v4.1 (gnomAD).

How is Methylmalonic acidemia with homocystinuria inherited?

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

ABCD4 p.Gln177Ter

c.529C>T · VCV4525942

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

methylmalonic aciduria and homocystinuria type cblC

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Overall
CADD	51.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD4
Protein: p.Gln177Ter
Coding: c.529C>T
MANE Select: NM_005050
Type: single nucleotide variant
Location: chr14:74296346 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB
Residue 177: the abc transmembrane type-1 domain

Full ABCD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methylmalonic aciduria and homocystinuria type cblC — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methylmalonic acidemia with homocystinuria (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: All ages

Similar variants

ABCD4 p.Arg432Gln Likely pathogenic ★★ same condition
ABCD4 p.Asn141Lys Pathogenic/Likely pathogenic ★★ same condition
ABCD4 p.Gln530Ter Pathogenic/Likely pathogenic ★★ same condition
ABCD4 c.1118+1G>A Likely pathogenic ★ same condition
ABCD4 p.Tyr319Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCD4 p.Ser416fs Pathogenic ★★ same condition
ABCD4 p.Gly183_Trp184insTer Pathogenic ★ same condition
ABCD4 p.Ser533fs 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/abcd4-p-gln177ter (accessed [today's date]).

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