Is ACLY p.Ile550= (c.1650C>T) pathogenic?

ACLY p.Ile550= (c.1650C>T) is classified Benign in ACLY (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-14). Rare (popmax 0.279%, afr).

How common is ACLY p.Ile550= (c.1650C>T) in the general population?

ACLY p.Ile550= (c.1650C>T) is rare (popmax 0.279%, afr) (gnomAD).

ACLY p.Ile550=

c.1650C>T · rs149936488 · VCV742001

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.279%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -3.4, phastCons 1
Overall
CADD	7.272	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.279% African / African-American · 209/75,000 alleles

Filtering AF 0.248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0134% 217/1,613,992 alleles · rare exomes 97/1,461,836 · genomes 120/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.279%	359
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.005%	19,993

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: ACLY
Protein: p.Ile550=
Coding: c.1650C>T
MANE Select: NM_001096
dbSNP: rs149936488
Type: single nucleotide variant
Location: chr17:41892399 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.61 · 36 PDB
Residue 550: a β-strand

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

Similar variants

ACLY p.Ile550Val Uncertain significance ★ ⚠ same residue
ACLY p.Gln314= Benign ★★ same type
ACLY p.Val286= Benign ★★ same type
ACLY p.Ala1032Thr Uncertain significance ★ ⚠ same type
ACLY p.Ala173Ser Uncertain significance ★ ⚠ same type
ACLY p.Ala173Thr Uncertain significance ★ ⚠ same type
ACLY p.Ala24Thr Uncertain significance ★ ⚠ same type
ACLY p.Ala432Thr 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/acly-p-ile550 (accessed [today's date]).

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