Is ACBD5 p.Pro323Gln (c.968C>A) pathogenic?

ACBD5 p.Pro323Gln (c.968C>A) is classified Benign in ACBD5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1003); Common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ACBD5 p.Pro323Gln (c.968C>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

ACBD5 p.Pro323Gln

Q: How common is ACBD5 p.Pro323Gln (c.968C>A) in the general population?

ACBD5 p.Pro323Gln (c.968C>A) is common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.968C>A · rs41314978 · VCV1165359

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.5%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	16.76	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P332Q vs ClinVar P323Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% East Asian · 4,696/44,870 alleles

Filtering AF 10.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.1%

Overall 0.592% 9,552/1,614,096 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	10.5%	10
South Asian	2.41%	42
Remaining individualsnot grpmax-eligible	1%	100
Middle Eastern	0.297%	337
Finnishnot grpmax-eligible	0.214%	467
European (non-Finnish)	0.145%	688
Admixed American	0.108%	923
African / African-American	0.108%	926
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,346

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: ACBD5
Protein: p.Pro323Gln
Coding: c.968C>A
MANE Select: NM_145698
dbSNP: rs41314978
Type: single nucleotide variant
Location: chr10:27211050 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB

Full ACBD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD5 p.Arg433Ter Pathogenic/Likely pathogenic ★★ same type
ACBD5 p.Ala182Thr Uncertain significance ★★ ⚠ same type
ACBD5 p.Arg384Trp Uncertain significance ★★ ⚠ same type
ACBD5 p.Arg415Trp Uncertain significance ★★ ⚠ same type
ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same type
ACBD5 p.Gln452His Uncertain significance ★★ ⚠ same type
ACBD5 p.Glu312Lys Uncertain significance ★★ ⚠ same type
ACBD5 p.Glu493Lys Uncertain significance ★★ ⚠ same type

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/acbd5-p-pro323gln (accessed [today's date]).

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