Is AACS p.Glu564Gln (c.1690G>C) pathogenic?

AACS p.Glu564Gln (c.1690G>C) is classified Benign in AACS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-04-05). AlphaMissense: likely benign (0.0941); Low-frequency (popmax 4.1%, afr).

How common is AACS p.Glu564Gln (c.1690G>C) in the general population?

AACS p.Glu564Gln (c.1690G>C) is low-frequency (popmax 4.1%, afr) (gnomAD).

What do computational predictors say about AACS p.Glu564Gln (c.1690G>C)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

AACS p.Glu564Gln

c.1690G>C · rs77320648 · VCV714324

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.1%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.23	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 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 77 kb · p 0.59 · regional, not allelic
Overall
CADD	22.9	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 4.1% African / African-American · 3,076/74,986 alleles

Filtering AF 3.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.93%

Overall 0.216% 3,479/1,613,716 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.1%	24
Admixed American	0.293%	341
Remaining individualsnot grpmax-eligible	0.269%	372
Middle Eastern	0.154%	650
European (non-Finnish)	0.0039%	25,652
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
South Asian	0.0033%	30,347

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: AACS
Protein: p.Glu564Gln
Coding: c.1690G>C
MANE Select: NM_023928
dbSNP: rs77320648
Type: single nucleotide variant
Location: chr12:125136673 (GRCh38)
Gene constraint: LOEUF 0.967 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09

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

Similar variants

AACS c.1881+8C>G Benign ★★ same type
AACS p.Arg107= Benign ★★ same type
AACS p.Ile430= Benign ★★ same type
AACS p.Phe276= Benign ★★ same type
AACS p.Ala169Thr Uncertain significance ★ ⚠ same type
AACS p.Ala271Pro Uncertain significance ★ ⚠ same type
AACS p.Ala349Val Uncertain significance ★ ⚠ same type
AACS p.Ala39Thr 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/aacs-p-glu564gln (accessed [today's date]).

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