Is ACAD10 p.Pro1025Ser (c.3073C>T) pathogenic?

ACAD10 p.Pro1025Ser (c.3073C>T) is classified Uncertain significance in ACAD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: ambiguous (0.3481); Very rare (popmax 0.00254%, nfe).

How common is ACAD10 p.Pro1025Ser (c.3073C>T) in the general population?

ACAD10 p.Pro1025Ser (c.3073C>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about ACAD10 p.Pro1025Ser (c.3073C>T)?

AlphaMissense predicts ambiguous (score 0.3481) — an in-silico prediction, not a clinical call.

ACAD10 p.Pro1025Ser

c.3073C>T · rs748666716 · VCV3134420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3481	ambiguous
REVEL	0.754	pathogenic-leaning
SaProt	LLR -12.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.85, phastCons 0.94
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.013 · regional, not allelic
Overall
CADD	23.1	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 0.00254% European (non-Finnish) · 30/1,179,346 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00226% 33/1,458,692 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,312
Admixed American	0.00167%	59,734
Remaining individualsnot grpmax-eligible	0.0016%	62,394
African / African-American	0.00133%	75,016

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.Pro1025Ser
Coding: c.3073C>T
MANE Select: NM_025247
dbSNP: rs748666716
Type: single nucleotide variant
Location: chr12:111756366 (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-pro1025ser (accessed [today's date]).

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