Is ACLY p.Glu237Lys (c.709G>A) pathogenic?

ACLY p.Glu237Lys (c.709G>A) is classified Uncertain significance in ACLY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-11). AlphaMissense: likely benign (0.2238); Very rare (popmax 0.00267%, afr).

How common is ACLY p.Glu237Lys (c.709G>A) in the general population?

ACLY p.Glu237Lys (c.709G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ACLY p.Glu237Lys (c.709G>A)?

AlphaMissense predicts likely benign (score 0.2238) — an in-silico prediction, not a clinical call.

ACLY p.Glu237Lys

c.709G>A · rs549516701 · VCV2277141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2238	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -11.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 30 kb · p 6.3e-16 · regional, not allelic
Overall
CADD	25.0	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 0.00267% African / African-American · 2/74,972 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,486
East Asian	0.00223%	44,852
Admixed American	0.00167%	60,004
European (non-Finnish)	0.000254%	393,311

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.Glu237Lys
Coding: c.709G>A
MANE Select: NM_001096
dbSNP: rs549516701
Type: single nucleotide variant
Location: chr17:41907480 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.61 · 36 PDB
Residue 237: the atp-grasp domain

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-glu237lys (accessed [today's date]).

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