Is ACADM p.Ile172Val (c.514A>G) pathogenic?

ACADM p.Ile172Val (c.514A>G) is classified Uncertain significance in ACADM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-08). AlphaMissense: likely benign (0.1909); Very rare (popmax 0.00329%, sas).

How common is ACADM p.Ile172Val (c.514A>G) in the general population?

ACADM p.Ile172Val (c.514A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ACADM p.Ile172Val (c.514A>G)?

AlphaMissense predicts likely benign (score 0.1909) — an in-silico prediction, not a clinical call.

ACADM p.Ile172Val

c.514A>G · rs1179642524 · VCV1303726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1909	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -8.88	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 1.7	GERP -3.7, phastCons 0.51
Regional constraint	o/e 0.98	unconstrained · MANE · 38 kb · p 0.63 · regional, not allelic
Overall
CADD	12.18	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 0.00329% South Asian · 3/91,060 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00093% 15/1,612,914 alleles · very rare exomes 14/1,460,688 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
European (non-Finnish)	0.00102%	98,266

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: ACADM
Protein: p.Ile172Val
Coding: c.514A>G
MANE Select: NM_000016
dbSNP: rs1179642524
Type: single nucleotide variant
Location: chr1:75740025 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.15 · 7 PDB

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

Similar variants

ACADM c.118+1G>T Likely pathogenic ★★ same type
ACADM c.1194+1G>A Pathogenic/Likely pathogenic ★★ same type
ACADM c.1194+2T>G Likely pathogenic ★★ same type
ACADM c.216+1G>A Pathogenic ★★ same type
ACADM c.216+1G>T Pathogenic/Likely pathogenic ★★ same type
ACADM c.216+2T>C Pathogenic ★★ same type
ACADM c.216+2T>G Pathogenic ★★ same type
ACADM c.217-1G>A 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/acadm-p-ile172val (accessed [today's date]).

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