Is ABCD4 p.Val60Ala (c.179T>C) pathogenic?

ABCD4 p.Val60Ala (c.179T>C) is classified Uncertain significance in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: ambiguous (0.5301); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD4 p.Val60Ala (c.179T>C)?

ABCD4 p.Val60Ala (c.179T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD4 p.Val60Ala (c.179T>C) in the general population?

ABCD4 p.Val60Ala (c.179T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD4 p.Val60Ala (c.179T>C)?

AlphaMissense predicts ambiguous (score 0.5301) — an in-silico prediction, not a clinical call.

ABCD4 p.Val60Ala

c.179T>C · rs2505857041 · VCV2550318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5301	ambiguous
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -11.41	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.79 · regional, not allelic
Overall
CADD	24.2	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

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.Val60Ala
Coding: c.179T>C
MANE Select: NM_005050
dbSNP: rs2505857041
Type: single nucleotide variant
Location: chr14:74299654 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB
Residue 60: the abc transmembrane type-1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCD4 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg252Gly Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg391Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg442Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln215Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln446Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gly566Ser Uncertain significance ★★ ⚠ same condition
ABCD4 p.Leu157Val Uncertain significance ★★ ⚠ 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-val60ala (accessed [today's date]).

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