Is ECD p.Ser440= (c.1320C>T) pathogenic?

ECD p.Ser440= (c.1320C>T) is classified Benign in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 5.68%, afr) — too common for a highly-penetrant pathogenic allele.

ECD p.Ser440=

Q: How common is ECD p.Ser440= (c.1320C>T) in the general population?

ECD p.Ser440= (c.1320C>T) is common (popmax 5.68%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1320C>T · rs34865820 · VCV780140

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.68%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.29, phastCons 1
Overall
CADD	9.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.68% African / African-American · 4,262/75,000 alleles

Filtering AF 5.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.48%

Overall 0.3% 4,844/1,614,050 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.68%	18
Remaining individualsnot grpmax-eligible	0.405%	247
Admixed American	0.288%	347
Middle Eastern	0.28%	357
South Asian	0.0176%	5,692
European (non-Finnish)	0.0103%	9,752
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802

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.Ser440=
Coding: c.1320C>T
MANE Select: NM_006304 · reported on NM_007265
dbSNP: rs34865820
Type: single nucleotide variant
Location: chr10:73139410 (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-ser440 (accessed [today's date]).

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