Is ASCC2 p.Lys562Arg (c.1685A>G) pathogenic?

ASCC2 p.Lys562Arg (c.1685A>G) is classified Likely benign in ASCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0583); Ultra-rare (popmax 0.079%, amr).

How common is ASCC2 p.Lys562Arg (c.1685A>G) in the general population?

ASCC2 p.Lys562Arg (c.1685A>G) is ultra-rare (popmax 0.079%, amr) (gnomAD).

What do computational predictors say about ASCC2 p.Lys562Arg (c.1685A>G)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

ASCC2 p.Lys562Arg

c.1685A>G · rs746785566 · VCV3130228

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.079%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -5.64	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 2	GERP -0.61, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 43 kb · p 0.00015 · regional, not allelic
Overall
CADD	14.27	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 0.079% Admixed American · 47/59,524 alleles

Filtering AF 0.061% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0546%

Overall 0.00427% 68/1,594,316 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.079%	1,266
Remaining individualsnot grpmax-eligible	0.00488%	20,490
European (non-Finnish)	0.00155%	64,680

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: ASCC2
Protein: p.Lys562Arg
Coding: c.1685A>G
MANE Select: NM_032204
dbSNP: rs746785566
Type: single nucleotide variant
Location: chr22:29800994 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15 · 2 PDB

Full ASCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCC2 p.Ala258Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala26Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala414Ser Uncertain significance ★ ⚠ same type
ASCC2 p.Ala457Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala50Thr Uncertain significance ★ ⚠ same type
ASCC2 p.Ala732Asp Uncertain significance ★ ⚠ same type
ASCC2 p.Ala735Val Uncertain significance ★ ⚠ same type
ASCC2 p.Ala738Gly 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/ascc2-p-lys562arg (accessed [today's date]).

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