Is ACLY p.Leu804= (c.2412C>T) pathogenic?

ACLY p.Leu804= (c.2412C>T) is classified Benign in ACLY (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-14). Rare (popmax 0.555%, afr).

How common is ACLY p.Leu804= (c.2412C>T) in the general population?

ACLY p.Leu804= (c.2412C>T) is rare (popmax 0.555%, afr) (gnomAD).

ACLY p.Leu804=

c.2412C>T · rs35022178 · VCV788605

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.555%, 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 -2.9	GERP -3.4
Overall
CADD	0.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.555% African / African-American · 408/73,474 alleles

Filtering AF 0.511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.493%

Overall 0.0299% 476/1,593,960 alleles · rare exomes 216/1,441,762 · genomes 260/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.555%	180
Remaining individualsnot grpmax-eligible	0.0455%	2,197
Admixed American	0.042%	2,383
East Asian	0.00467%	21,433
South Asian	0.00226%	44,324
European (non-Finnish)	0.00103%	97,556

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.Leu804=
Coding: c.2412C>T
MANE Select: NM_001096
dbSNP: rs35022178
Type: single nucleotide variant
Location: chr17:41878178 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.61 · 36 PDB
Residue 804: an α-helix

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

Similar variants

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
ACLY p.Ala461Val 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-leu804 (accessed [today's date]).

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