Is AACS p.Gly319Ser (c.955G>A) pathogenic?

AACS p.Gly319Ser (c.955G>A) is classified Uncertain significance in AACS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.1578); Rare (popmax 0.104%, afr).

How common is AACS p.Gly319Ser (c.955G>A) in the general population?

AACS p.Gly319Ser (c.955G>A) is rare (popmax 0.104%, afr) (gnomAD).

What do computational predictors say about AACS p.Gly319Ser (c.955G>A)?

AlphaMissense predicts likely benign (score 0.1578) — an in-silico prediction, not a clinical call.

AACS p.Gly319Ser

c.955G>A · rs143681355 · VCV3128550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1578 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1578	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -10.41	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 1.5	GERP -0.84, phastCons 0.88
Regional constraint	o/e 0.98	unconstrained · MANE · 77 kb · p 0.59 · regional, not allelic
Overall
CADD	17.9	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 0.104% African / African-American · 78/74,890 alleles

Filtering AF 0.0855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00688% 111/1,613,262 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	960
Admixed American	0.04%	2,499
Middle Eastern	0.0164%	6,082
East Asian	0.00446%	22,431
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)	0.000339%	294,936

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.Gly319Ser
Coding: c.955G>A
MANE Select: NM_023928
dbSNP: rs143681355
Type: single nucleotide variant
Location: chr12:125114516 (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-gly319ser (accessed [today's date]).

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