Is ACADL p.Ala3Ser (c.7G>T) pathogenic?

ACADL p.Ala3Ser (c.7G>T) is classified Likely benign in ACADL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-23). AlphaMissense: likely benign (0.126); Low-frequency (popmax 1.16%, eas); Associated with ACADL-related disorder.

What condition is associated with ACADL p.Ala3Ser (c.7G>T)?

ACADL p.Ala3Ser (c.7G>T) is associated with ACADL-related disorder (ClinVar).

How common is ACADL p.Ala3Ser (c.7G>T) in the general population?

ACADL p.Ala3Ser (c.7G>T) is low-frequency (popmax 1.16%, eas) (gnomAD).

What do computational predictors say about ACADL p.Ala3Ser (c.7G>T)?

AlphaMissense predicts likely benign (score 0.126) — an in-silico prediction, not a clinical call.

ACADL p.Ala3Ser

c.7G>T · rs763274790 · VCV3032185

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.126 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.16%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACADL-related disorder

Computational evidence

Protein change
AlphaMissense	0.126	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -7.49	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 -0.32	GERP -3.5, phastCons 0.002
Regional constraint	o/e 0.92	unconstrained · MANE · 36 kb · p 0.07 · regional, not allelic
Overall
CADD	7.174	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 1.16% East Asian · 484/41,550 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0351% 547/1,556,570 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.16%	86
South Asian	0.02%	5,002
Middle Eastern	0.0185%	5,400
Remaining individualsnot grpmax-eligible	0.0099%	10,098
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,720
European (non-Finnish)	0.0032%	31,274
African / African-American	0.00136%	73,330

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: ACADL
Protein: p.Ala3Ser
Coding: c.7G>T
MANE Select: NM_001608
dbSNP: rs763274790
Type: single nucleotide variant
Location: chr2:210225257 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.09 · 3 PDB

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

Disease context

ACADL-related disorder

Similar variants

ACADL p.Ile170Val Uncertain significance ★★ ⚠ same condition
ACADL c.871-2A>G Uncertain significance ★ same condition
ACADL p.Cys166Tyr Uncertain significance ★ ⚠ same condition
ACADL p.His228Arg Uncertain significance ★ ⚠ same condition
ACADL p.Tyr282Cys Uncertain significance ⚠ same condition
ACADL c.1112+5G>A Likely benign same condition
ACADL c.1199+9A>G Likely benign same condition
ACADL c.234-4G>A Likely benign 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/acadl-p-ala3ser (accessed [today's date]).

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