Is ECPAS p.Ser699Cys (c.2095A>T) pathogenic?

ECPAS p.Ser699Cys (c.2095A>T) is classified Uncertain significance in ECPAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). Very rare (popmax 0.000256%, nfe).

How common is ECPAS p.Ser699Cys (c.2095A>T) in the general population?

ECPAS p.Ser699Cys (c.2095A>T) is very rare (popmax 0.000256%, nfe) (gnomAD).

ECPAS p.Ser699Cys

c.2095A>T · VCV4016112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000256%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.294	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 28 kb · p 8.8e-08 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000256% European (non-Finnish) · 3/1,172,716 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000209% 3/1,435,552 alleles · very rare

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: ECPAS
Protein: p.Ser699Cys
Coding: c.2095A>T
MANE Select: NM_001364929
Type: single nucleotide variant
Location: chr9:111412133 (GRCh38)
Gene constraint: LOEUF 0.316 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.03

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

Similar variants

ECPAS p.Ser699Gly Uncertain significance ★ same residue
ECPAS c.270+1G>T Uncertain significance ★ same type
ECPAS c.-128G>A Uncertain significance ★ same type
ECPAS c.-128G>C Uncertain significance ★ same type
ECPAS c.-138C>T Uncertain significance ★ same type
ECPAS c.-150C>T Uncertain significance ★ same type
ECPAS c.-152C>T Uncertain significance ★ same type
ECPAS c.-176C>G 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/ecpas-p-ser699cys (accessed [today's date]).

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