Is ECT2 p.Pro481= (c.1443A>G) pathogenic?

ECT2 p.Pro481= (c.1443A>G) is classified Benign in ECT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-31). Common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele.

ECT2 p.Pro481=

Q: How common is ECT2 p.Pro481= (c.1443A>G) in the general population?

ECT2 p.Pro481= (c.1443A>G) is common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1443A>G · rs61747133 · VCV775928

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.98%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -3
Overall
CADD	1.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.98% African / African-American · 5,984/74,942 alleles

Filtering AF 7.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.75%

Overall 0.424% 6,843/1,613,410 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.98%	13
Remaining individualsnot grpmax-eligible	0.536%	187
Admixed American	0.487%	205
Middle Eastern	0.38%	263
East Asian	0.029%	3,450
South Asian	0.0242%	4,137
European (non-Finnish)	0.0148%	6,779

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: ECT2
Protein: p.Pro481=
Coding: c.1443A>G
MANE Select: NM_001258315
dbSNP: rs61747133
Type: single nucleotide variant
Location: chr3:172773917 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB
Residue 481: the dh domain; an α-helix

Full ECT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECT2 p.His912Arg Uncertain significance ★★ ⚠ same type
ECT2 p.Pro236Ala Uncertain significance ★★ ⚠ same type
ECT2 c.1069-2A>G Uncertain significance ★ same type
ECT2 p.Ala258Thr Uncertain significance ★ ⚠ same type
ECT2 p.Ala850Thr Uncertain significance ★ ⚠ same type
ECT2 p.Arg169Cys Uncertain significance ★ ⚠ same type
ECT2 p.Arg194Met Uncertain significance ★ ⚠ same type
ECT2 p.Arg228Lys 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/ect2-p-pro481 (accessed [today's date]).

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