Is ACBD5 p.Ser41Tyr (c.122C>A) pathogenic?

ACBD5 p.Ser41Tyr (c.122C>A) is classified Uncertain significance in ACBD5 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-13). AlphaMissense: likely benign (0.2852); Absent from gnomAD v4.1; Associated with retinal dystrophy with leukodystrophy.

What condition is associated with ACBD5 p.Ser41Tyr (c.122C>A)?

ACBD5 p.Ser41Tyr (c.122C>A) is associated with retinal dystrophy with leukodystrophy (ClinVar).

How common is ACBD5 p.Ser41Tyr (c.122C>A) in the general population?

ACBD5 p.Ser41Tyr (c.122C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACBD5 p.Ser41Tyr (c.122C>A)?

AlphaMissense predicts likely benign (score 0.2852) — an in-silico prediction, not a clinical call.

ACBD5 p.Ser41Tyr

c.122C>A · rs2065329219 · VCV969184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinal dystrophy with leukodystrophy

Computational evidence

Protein change
AlphaMissense	0.2852	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -9.99	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 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S39Y vs ClinVar S41Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACBD5
Protein: p.Ser41Tyr
Coding: c.122C>A
MANE Select: NM_145698
dbSNP: rs2065329219
Type: single nucleotide variant
Location: chr10:27240378 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 41: the acb domain; an α-helix

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

Disease context

retinal dystrophy with leukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same condition
ACBD5 c.15+54G>T Benign ★★ same condition
ACBD5 c.491-51A>G Benign ★★ same condition
ACBD5 p.Pro173= Benign ★★ same condition
ACBD5 c.936+1G>A Likely pathogenic ★ same condition
ACBD5 c.1565+2T>A Uncertain significance ★ same condition
ACBD5 p.Glu393Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
ACBD5 p.Leu476Ser 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/acbd5-p-ser41tyr (accessed [today's date]).

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