Is ASCC3 p.Pro1980= (c.5940G>A) pathogenic?

ASCC3 p.Pro1980= (c.5940G>A) is classified Likely benign in ASCC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-01). Low-frequency (popmax 1.19%, afr).

How common is ASCC3 p.Pro1980= (c.5940G>A) in the general population?

ASCC3 p.Pro1980= (c.5940G>A) is low-frequency (popmax 1.19%, afr) (gnomAD).

ASCC3 p.Pro1980=

c.5940G>A · VCV4533974

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, afr)

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 -0.31	GERP -4.2
Overall
CADD	1.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.19% African / African-American · 895/74,990 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.0614% 991/1,613,644 alleles · low-frequency exomes 479/1,461,410 · genomes 512/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.19%	84
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Middle Eastern	0.0495%	2,020
Admixed American	0.0467%	2,141
South Asian	0.00439%	22,766
East Asian	0.00223%	44,876
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	0.00127%	78,645

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: ASCC3
Protein: p.Pro1980=
Coding: c.5940G>A
MANE Select: NM_006828
Type: single nucleotide variant
Location: chr6:100516315 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.93 · 2 PDB
Residue 1980: a UniProt-annotated variant site (in mrt81; uncertain significance); the sec63 2 domain

Full ASCC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCC3 p.Pro1980Leu Uncertain significance ★ ⚠ same residue
ASCC3 c.1597-2A>G Likely pathogenic ★★ same type
ASCC3 c.1596+1G>T Uncertain significance ★★ same type
ASCC3 p.Ala1186Val Uncertain significance ★★ ⚠ same type
ASCC3 p.Ala94Val Uncertain significance ★★ ⚠ same type
ASCC3 p.Arg1808His Uncertain significance ★★ ⚠ same type
ASCC3 p.Arg1835Cys Uncertain significance ★★ ⚠ same type
ASCC3 p.Arg630Cys 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/ascc3-p-pro1980 (accessed [today's date]).

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