Is ASCL1 p.Pro27= (c.81C>T) pathogenic?

ASCL1 p.Pro27= (c.81C>T) is classified Likely benign in ASCL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-26). Very rare (popmax 0.00132%, sas).

How common is ASCL1 p.Pro27= (c.81C>T) in the general population?

ASCL1 p.Pro27= (c.81C>T) is very rare (popmax 0.00132%, sas) (gnomAD).

ASCL1 p.Pro27=

c.81C>T · VCV4918203

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00132%, sas)

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 -1.4	GERP -2.1
Overall
CADD	6.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00132% South Asian · 1/75,706 alleles

Overall 0.000151% 2/1,320,646 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00132%	75,706
European (non-Finnish)	8.95e-05%	1,117,249

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: ASCL1
Protein: p.Pro27=
Coding: c.81C>T
MANE Select: NM_004316
Type: single nucleotide variant
Location: chr12:102958325 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 68.22

Full ASCL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCL1 c.-197T>C Benign ★★ same type
ASCL1 p.Ala41= Benign/Likely benign ★★ same type
ASCL1 p.Ala41Ser Likely benign ★★ ⚠ same type
ASCL1 p.Ala46= Likely benign ★★ same type
ASCL1 p.Val209= Benign ★★ same type
ASCL1 p.Ala139Val Uncertain significance ★ ⚠ same type
ASCL1 p.Ala39Thr Uncertain significance ★ ⚠ same type
ASCL1 p.Ala43Thr 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/ascl1-p-pro27 (accessed [today's date]).

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