Is ASCC3 p.Ala305Pro (c.913G>C) pathogenic?

ASCC3 p.Ala305Pro (c.913G>C) is classified Uncertain significance in ASCC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.1042); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASCC3 p.Ala305Pro (c.913G>C)?

ASCC3 p.Ala305Pro (c.913G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ASCC3 p.Ala305Pro (c.913G>C) in the general population?

ASCC3 p.Ala305Pro (c.913G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ASCC3 p.Ala305Pro (c.913G>C)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

ASCC3 p.Ala305Pro

c.913G>C · rs768860627 · VCV2479454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.71	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 1.1	GERP 0.74, phastCons 0.16
Regional constraint	o/e 1.00	unconstrained · MANE · 68 kb · p 0.97 · regional, not allelic
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0011% South Asian · 1/91,004 alleles

Overall 0.000343% 5/1,458,666 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00482%	20,768
South Asiangrpmax	0.0011%	91,004
European (non-Finnish)	8.49e-05%	1,178,441

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala305Pro
Coding: c.913G>C
MANE Select: NM_006828
dbSNP: rs768860627
Type: single nucleotide variant
Location: chr6:100805769 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.93 · 2 PDB
Residue 305: the 'required for interaction with ascc2' region

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.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
ASCC3 p.Glu344Gly 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-ala305pro (accessed [today's date]).

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