Is AACS p.Arg107= (c.319C>A) pathogenic?

AACS p.Arg107= (c.319C>A) is classified Benign in AACS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-18). Common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele.

AACS p.Arg107=

Q: How common is AACS p.Arg107= (c.319C>A) in the general population?

AACS p.Arg107= (c.319C>A) is common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.319C>A · rs77474358 · VCV778668

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.76%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.46	GERP -3.2
Overall
CADD	6.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.76% African / African-American · 6,566/74,982 alleles

Filtering AF 8.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.51%

Overall 0.491% 7,919/1,614,060 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.76%	11
Middle Eastern	0.973%	103
Remaining individualsnot grpmax-eligible	0.757%	132
Admixed American	0.596%	168
Ashkenazi Jewishnot grpmax-eligible	0.372%	269
European (non-Finnish)	0.0283%	3,533
South Asian	0.0209%	4,794

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.Arg107=
Coding: c.319C>A
MANE Select: NM_023928
dbSNP: rs77474358
Type: single nucleotide variant
Location: chr12:125076572 (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 p.Arg107Trp Uncertain significance ★ ⚠ same residue
AACS c.1881+8C>G 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-arg107 (accessed [today's date]).

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