Is ECD p.Thr260= (c.780A>G) pathogenic?

ECD p.Thr260= (c.780A>G) is classified Likely benign in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0349%, mid).

How common is ECD p.Thr260= (c.780A>G) in the general population?

ECD p.Thr260= (c.780A>G) is ultra-rare (popmax 0.0349%, mid) (gnomAD).

ECD p.Thr260=

c.780A>G · rs150282030 · VCV2640581

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, mid)

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 -2.7	GERP -1.9
Overall
CADD	2.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0349% Middle Eastern · 2/5,728 alleles

Filtering AF 0.00613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00254%

Overall 0.000565% 9/1,592,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0349%	2,864
Remaining individualsnot grpmax-eligible	0.00325%	30,743
African / African-American	0.00135%	74,166
European (non-Finnish)	0.000342%	292,263

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: ECD
Protein: p.Thr260=
Coding: c.780A>G
MANE Select: NM_006304 · reported on NM_007265
dbSNP: rs150282030
Type: single nucleotide variant
Location: chr10:73154259 (GRCh38)
Structure: AlphaFold pLDDT 69.87 · 140 PDB

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

Similar variants

ECD p.Ala121Gly Uncertain significance ★ ⚠ same type
ECD p.Ala122Ser Uncertain significance ★ ⚠ same type
ECD p.Ala150Thr Uncertain significance ★ ⚠ same type
ECD p.Ala234Ser Uncertain significance ★ ⚠ same type
ECD p.Ala329Val Uncertain significance ★ ⚠ same type
ECD p.Arg188Leu Uncertain significance ★ ⚠ same type
ECD p.Arg244Gln Uncertain significance ★ ⚠ same type
ECD p.Arg281Gln 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/ecd-p-thr260 (accessed [today's date]).

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