Is ACADS p.Arg14His (c.41G>A) pathogenic?

ACADS p.Arg14His (c.41G>A) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: ambiguous (0.359); Very rare (popmax 0.00279%, afr).

How common is ACADS p.Arg14His (c.41G>A) in the general population?

ACADS p.Arg14His (c.41G>A) is very rare (popmax 0.00279%, afr) (gnomAD).

What do computational predictors say about ACADS p.Arg14His (c.41G>A)?

AlphaMissense predicts ambiguous (score 0.359) — an in-silico prediction, not a clinical call.

ACADS p.Arg14His

c.41G>A · rs937772855 · VCV2683218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00279%, afr)

Computational evidence

Protein change
AlphaMissense	0.359	ambiguous
REVEL	0.379	indeterminate
SaProt	LLR -10.00	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.72, phastCons 0.14
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	18.59	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 0.00279% African / African-American · 2/71,810 alleles

Filtering AF 0.000777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000616%

Overall 0.00116% 18/1,552,030 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00279%	35,905
Remaining individualsnot grpmax-eligible	0.00165%	60,462
European (non-Finnish)	0.00129%	77,231

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: ACADS
Protein: p.Arg14His
Coding: c.41G>A
MANE Select: NM_000017
dbSNP: rs937772855
Type: single nucleotide variant
Location: chr12:120725926 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB

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

Similar variants

ACADS p.Arg14Gly Uncertain significance ★ ⚠ same residue
ACADS c.211-2A>G Likely pathogenic ★★ same type
ACADS c.625-1G>A Likely pathogenic ★★ same type
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same type
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same type
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same type
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same type
ACADS p.Arg325Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/acads-p-arg14his (accessed [today's date]).

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