Is ACBD5 p.Ser88Pro (c.262T>C) pathogenic?

ACBD5 p.Ser88Pro (c.262T>C) is classified Conflicting classifications of pathogenicity in ACBD5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0803); Rare (popmax 0.614%, sas).

How common is ACBD5 p.Ser88Pro (c.262T>C) in the general population?

ACBD5 p.Ser88Pro (c.262T>C) is rare (popmax 0.614%, sas) (gnomAD).

What do computational predictors say about ACBD5 p.Ser88Pro (c.262T>C)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

ACBD5 p.Ser88Pro

c.262T>C · rs199700938 · VCV546639

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.614%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -4.74	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 6.1	GERP 0.53, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	17.12	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 S86P vs ClinVar S88P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.614% South Asian · 559/91,086 alleles

Filtering AF 0.572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.555%

Overall 0.0389% 628/1,614,044 alleles · rare exomes 588/1,461,724 · genomes 40/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.614%	163
Remaining individualsnot grpmax-eligible	0.0512%	1,953
European (non-Finnish)	0.00297%	33,713
East Asian	0.00223%	44,830
Finnishnot grpmax-eligible	0.00156%	64,028

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.Ser88Pro
Coding: c.262T>C
MANE Select: NM_145698
dbSNP: rs199700938
Type: single nucleotide variant
Location: chr10:27235132 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 86 UniProt numbering: the acb domain; an α-helix

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-ser88pro (accessed [today's date]).

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