Is ECPAS p.Arg1423Gln (c.4268G>A) pathogenic?

ECPAS p.Arg1423Gln (c.4268G>A) is classified Uncertain significance in ECPAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). Very rare (popmax 0.00246%, nfe).

How common is ECPAS p.Arg1423Gln (c.4268G>A) in the general population?

ECPAS p.Arg1423Gln (c.4268G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

ECPAS p.Arg1423Gln

c.4268G>A · rs947043667 · VCV3087063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.373	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 48 kb · p 1.8e-10 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,480 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00192% 31/1,613,294 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
European (non-Finnish)grpmax	0.00246%	40,672
African / African-American	0.00134%	74,876

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1423Gln
Coding: c.4268G>A
MANE Select: NM_001364929
dbSNP: rs947043667
Type: single nucleotide variant
Location: chr9:111373316 (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 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
ECPAS c.-186C>T 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-arg1423gln (accessed [today's date]).

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