Is ABCD4 p.Val109Met (c.325G>A) pathogenic?

ABCD4 p.Val109Met (c.325G>A) is classified Uncertain significance in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.4709); Very rare (popmax 0.000932%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD4 p.Val109Met (c.325G>A)?

ABCD4 p.Val109Met (c.325G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD4 p.Val109Met (c.325G>A) in the general population?

ABCD4 p.Val109Met (c.325G>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about ABCD4 p.Val109Met (c.325G>A)?

AlphaMissense predicts ambiguous (score 0.4709) — an in-silico prediction, not a clinical call.

ABCD4 p.Val109Met

c.325G>A · rs768088632 · VCV2394642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4709	ambiguous
REVEL	0.783	moderately pathogenic-leaning
SaProt	LLR -6.95	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.79 · regional, not allelic
Overall
CADD	25.8	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 0.000932% European (non-Finnish) · 11/1,179,992 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,852 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: ABCD4
Protein: p.Val109Met
Coding: c.325G>A
MANE Select: NM_005050
dbSNP: rs768088632
Type: single nucleotide variant
Location: chr14:74298030 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB
Residue 109: 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-val109met (accessed [today's date]).

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