Is ASCC3 p.Ser766Pro (c.2296T>C) pathogenic?

ASCC3 p.Ser766Pro (c.2296T>C) is classified Uncertain significance in ASCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.9841); Very rare (popmax 0.0067%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASCC3 p.Ser766Pro (c.2296T>C)?

ASCC3 p.Ser766Pro (c.2296T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASCC3 p.Ser766Pro (c.2296T>C) in the general population?

ASCC3 p.Ser766Pro (c.2296T>C) is very rare (popmax 0.0067%, nfe) (gnomAD).

What do computational predictors say about ASCC3 p.Ser766Pro (c.2296T>C)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

ASCC3 p.Ser766Pro

c.2296T>C · rs773368984 · VCV2469340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 291 kb · p 5e-15 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0067% European (non-Finnish) · 79/1,179,162 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00527% 85/1,612,664 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,926
Remaining individualsnot grpmax-eligible	0.00481%	20,805
Finnishnot grpmax-eligible	0.00469%	21,320

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.Ser766Pro
Coding: c.2296T>C
MANE Select: NM_006828
dbSNP: rs773368984
Type: single nucleotide variant
Location: chr6:100662527 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.93 · 2 PDB
Residue 766: the helicase c-terminal 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASCC3 p.Ser766Leu Uncertain significance ★ ⚠ same residue
ASCC3 p.Ala1186Val Uncertain significance ★★ ⚠ same condition
ASCC3 p.Ala94Val Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg1808His Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg1835Cys Uncertain significance ★★ ⚠ same condition
ASCC3 p.Arg630Cys Uncertain significance ★★ ⚠ same condition
ASCC3 p.Asn1607Ser Uncertain significance ★★ ⚠ same condition
ASCC3 p.Asp292Asn Uncertain significance ★★ ⚠ same condition

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-ser766pro (accessed [today's date]).

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