Is ACAD10 p.Ala978Val (c.2933C>T) pathogenic?

ACAD10 p.Ala978Val (c.2933C>T) is classified Uncertain significance in ACAD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-28). AlphaMissense: likely pathogenic (0.7793); Ultra-rare (popmax 0.0156%, eas).

How common is ACAD10 p.Ala978Val (c.2933C>T) in the general population?

ACAD10 p.Ala978Val (c.2933C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ACAD10 p.Ala978Val (c.2933C>T)?

AlphaMissense predicts likely pathogenic (score 0.7793) — an in-silico prediction, not a clinical call.

ACAD10 p.Ala978Val

c.2933C>T · rs775118172 · VCV2530459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7793	likely pathogenic
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -13.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.013 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,786 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00048% 7/1,458,424 alleles · ultra-rare

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: ACAD10
Protein: p.Ala978Val
Coding: c.2933C>T
MANE Select: NM_025247
dbSNP: rs775118172
Type: single nucleotide variant
Location: chr12:111753887 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.83

Full ACAD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD10 p.Ala1000Ser Uncertain significance ★ ⚠ same type
ACAD10 p.Ala1014Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala1048Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala222Ser Uncertain significance ★ ⚠ same type
ACAD10 p.Ala44Val Uncertain significance ★ ⚠ same type
ACAD10 p.Ala593Thr Uncertain significance ★ ⚠ same type
ACAD10 p.Ala597Thr Uncertain significance ★ ⚠ same type
ACAD10 p.Ala910Val 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/acad10-p-ala978val (accessed [today's date]).

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