Is AACS p.Cys40Tyr (c.119G>A) pathogenic?

AACS p.Cys40Tyr (c.119G>A) is classified Uncertain significance in AACS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.0721); Absent from gnomAD v4.1.

How common is AACS p.Cys40Tyr (c.119G>A) in the general population?

AACS p.Cys40Tyr (c.119G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AACS p.Cys40Tyr (c.119G>A)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

AACS p.Cys40Tyr

c.119G>A · VCV4145368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,538,704)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -3.44	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 4	GERP 0.58, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 77 kb · p 0.59 · regional, not allelic
Overall
CADD	18.4	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

No allele count reported in gnomAD v4.1 (AN 1,538,704). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AACS
Protein: p.Cys40Tyr
Coding: c.119G>A
MANE Select: NM_023928
Type: single nucleotide variant
Location: chr12:125065703 (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.Glu564Gln 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

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-cys40tyr (accessed [today's date]).

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