Is ACBD6 p.Arg202Gln (c.605G>A) pathogenic?

ACBD6 p.Arg202Gln (c.605G>A) is classified Uncertain significance in ACBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: ambiguous (0.5328); Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACBD6 p.Arg202Gln (c.605G>A)?

ACBD6 p.Arg202Gln (c.605G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD6 p.Arg202Gln (c.605G>A) in the general population?

ACBD6 p.Arg202Gln (c.605G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about ACBD6 p.Arg202Gln (c.605G>A)?

AlphaMissense predicts ambiguous (score 0.5328) — an in-silico prediction, not a clinical call.

ACBD6 p.Arg202Gln

c.605G>A · VCV4828594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5328 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5328	ambiguous
REVEL	0.535	indeterminate
SaProt	LLR -9.33	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 214 kb · p 0.89 · regional, not allelic
Overall
CADD	28.5	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 0.0267% Admixed American · 16/59,996 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00242% 39/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
African / African-American	0.0213%	4,687
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,870
European (non-Finnish)	0.000339%	294,984

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.Arg202Gln
Coding: c.605G>A
MANE Select: NM_032360
Type: single nucleotide variant
Location: chr1:180397574 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB
Residue 202: 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.Met286Thr Uncertain significance ★★ ⚠ same condition
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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-arg202gln (accessed [today's date]).

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