Is ACBD6 p.Asp104Ala (c.311A>C) pathogenic?

ACBD6 p.Asp104Ala (c.311A>C) is classified Uncertain significance in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: ambiguous (0.3466); Rare (popmax 0.743%, mid); Associated with Inborn genetic diseases.

What condition is associated with ACBD6 p.Asp104Ala (c.311A>C)?

ACBD6 p.Asp104Ala (c.311A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD6 p.Asp104Ala (c.311A>C) in the general population?

ACBD6 p.Asp104Ala (c.311A>C) is rare (popmax 0.743%, mid) (gnomAD).

What do computational predictors say about ACBD6 p.Asp104Ala (c.311A>C)?

AlphaMissense predicts ambiguous (score 0.3466) — an in-silico prediction, not a clinical call.

ACBD6 p.Asp104Ala

c.311A>C · rs752535782 · VCV2371801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3466 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.743%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3466	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 214 kb · p 0.89 · regional, not allelic
Overall
CADD	24.1	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 0.743% Middle Eastern · 45/6,060 alleles

Filtering AF 0.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.00892% 144/1,614,050 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.743%	135
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.00695%	14,390
African / African-American	0.004%	25,008
South Asian	0.00329%	30,360
Admixed American	0.00167%	60,022

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.Asp104Ala
Coding: c.311A>C
MANE Select: NM_032360
dbSNP: rs752535782
Type: single nucleotide variant
Location: chr1:180492342 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 104: the acb domain; a UniProt-annotated variant site (in nedpm; 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

LHX4 p.Ala354Val Uncertain significance ★★ ⚠ same condition
LHX4 p.Arg161Gln Uncertain significance ★★ ⚠ same condition
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-asp104ala (accessed [today's date]).

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