Is ACBD6 p.Ala234Val (c.701C>T) pathogenic?

ACBD6 p.Ala234Val (c.701C>T) is classified Uncertain significance in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: ambiguous (0.4866); Rare (popmax 0.125%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACBD6 p.Ala234Val (c.701C>T)?

ACBD6 p.Ala234Val (c.701C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD6 p.Ala234Val (c.701C>T) in the general population?

ACBD6 p.Ala234Val (c.701C>T) is rare (popmax 0.125%, eas) (gnomAD).

What do computational predictors say about ACBD6 p.Ala234Val (c.701C>T)?

AlphaMissense predicts ambiguous (score 0.4866) — an in-silico prediction, not a clinical call.

ACBD6 p.Ala234Val

c.701C>T · VCV3261376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4866 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4866	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 214 kb · p 0.89 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.125% East Asian · 56/44,852 alleles

Filtering AF 0.0987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0893%

Overall 0.00397% 64/1,612,916 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.125%	801
Finnishnot grpmax-eligible	0.00782%	12,792
South Asian	0.0011%	90,942
European (non-Finnish)	0.00017%	589,803

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: ACBD6
Protein: p.Ala234Val
Coding: c.701C>T
MANE Select: NM_032360
Type: single nucleotide variant
Location: chr1:180288511 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 234: a UniProt-annotated variant site (in nedpm; pathogenic); a UniProt-annotated variant site (in nedpm; likely pathogenic)

Full ACBD6 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

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LHX4 p.Gly283Arg Uncertain significance ★★ ⚠ same condition
LHX4 p.His387Gln Uncertain significance ★★ ⚠ same condition
LHX4 p.Leu338Trp Uncertain significance ★★ ⚠ same condition
LHX4 p.Met286Thr Uncertain significance ★★ ⚠ same condition
LHX4 p.Ser230Asn Uncertain significance ★★ ⚠ same condition
LHX4 p.Ser318Leu 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/acbd6-p-ala234val (accessed [today's date]).

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