Is ANAPC1 p.Pro1447= (c.4341G>A) pathogenic?

ANAPC1 p.Pro1447= (c.4341G>A) is classified Benign in ANAPC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-08). Common (popmax 26.5%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Rothmund-Thomson syndrome type 1.

What condition is associated with ANAPC1 p.Pro1447= (c.4341G>A)?

ANAPC1 p.Pro1447= (c.4341G>A) is associated with Rothmund-Thomson syndrome type 1 (ClinVar).

How is Rothmund-Thomson syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ANAPC1 p.Pro1447=

Q: How common is ANAPC1 p.Pro1447= (c.4341G>A) in the general population?

ANAPC1 p.Pro1447= (c.4341G>A) is common (popmax 26.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4341G>A · rs56780932 · VCV769572

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 26.5%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Rothmund-Thomson syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.156	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.3, phastCons 1
Overall
CADD	13.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.5% Middle Eastern · 1,512/5,714 alleles

Filtering AF 25.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.9%

Overall 20.1% 305,491/1,516,528 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	26.5%	4
European (non-Finnish)	21.7%	5
Ashkenazi Jewishnot grpmax-eligible	21.1%	5
South Asian	20.6%	5
Remaining individualsnot grpmax-eligible	20.2%	5
Amishnot grpmax-eligible	18.3%	5
Admixed American	16%	6
Finnishnot grpmax-eligible	15.7%	6
East Asian	14.7%	7
African / African-American	5.75%	17

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: ANAPC1
Protein: p.Pro1447=
Coding: c.4341G>A
MANE Select: NM_022662
dbSNP: rs56780932
Type: single nucleotide variant
Location: chr2:111794850 (GRCh38)
Gene constraint: LOEUF 0.273 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.46 · 21 PDB

Full ANAPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rothmund-Thomson syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rothmund-Thomson syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ANAPC1 p.Gly79Glu Uncertain significance ★★ ⚠ same condition
ANAPC1 c.1651-23A>G Benign ★★ same condition
ANAPC1 c.685+25A>G Benign ★★ same condition
ANAPC1 c.*2C>T Benign ★★ same condition
ANAPC1 p.Ile1791= Benign ★★ same condition
ANAPC1 p.Leu597= Benign ★★ same condition
ANAPC1 p.Ser227= Benign/Likely benign ★★ same condition
ANAPC1 p.Thr838Met Benign/Likely benign ★★ ⚠ 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/anapc1-p-pro1447 (accessed [today's date]).

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