Is ACAD10 p.Arg172Gln (c.515G>A) pathogenic?

ACAD10 p.Arg172Gln (c.515G>A) is classified Uncertain significance in ACAD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0801); Ultra-rare (popmax 0.033%, mid).

How common is ACAD10 p.Arg172Gln (c.515G>A) in the general population?

ACAD10 p.Arg172Gln (c.515G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ACAD10 p.Arg172Gln (c.515G>A)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

ACAD10 p.Arg172Gln

c.515G>A · rs200380265 · VCV2557994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 3.4	GERP 0.91, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 64 kb · p 0.013 · regional, not allelic
Overall
CADD	21.6	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00173% 28/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0048%	20,835
African / African-American	0.004%	25,005
South Asian	0.00329%	30,355
European (non-Finnish)	0.00144%	69,411

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.Arg172Gln
Coding: c.515G>A
MANE Select: NM_025247
dbSNP: rs200380265
Type: single nucleotide variant
Location: chr12:111705916 (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-arg172gln (accessed [today's date]).

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