Is CA4 p.Ter313ProextTer? (c.881_935dup) pathogenic?

CA4 p.Ter313ProextTer? (c.881935dup) is classified Uncertain significance in CA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Very rare (popmax 0.00017%, nfe).

How common is CA4 p.Ter313ProextTer? (c.881_935dup) in the general population?

CA4 p.Ter313ProextTer? (c.881_935dup) is very rare (popmax 0.00017%, nfe) (gnomAD).

CA4 p.Ter313ProextTer?

c.881_935dup · rs1567733151 · VCV1006753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.89	GERP 0.13

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,390 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,710 alleles · very rare exomes 1/1,459,514 · genomes 1/152,196 · joint denominator

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: CA4
Protein: p.Ter313ProextTer?
Coding: c.881_935dup
MANE Select: NM_000717
dbSNP: rs1567733151
Type: Duplication
Location: chr17:60159364 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB

Full CA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA4 p.Ter313Arg Likely pathogenic ★ same residue
CA4 p.Gly285fs Uncertain significance ★★ same type
CA4 c.269-11dup Likely benign ★ 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/ca4-p-ter313proextter (accessed [today's date]).

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