Is ATRIP p.Ser31fs (c.89dup) pathogenic?

ATRIP p.Ser31fs (c.89dup) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-13). Very rare (popmax 0.00284%, eas).

How common is ATRIP p.Ser31fs (c.89dup) in the general population?

ATRIP p.Ser31fs (c.89dup) is very rare (popmax 0.00284%, eas) (gnomAD).

ATRIP p.Ser31fs

c.89dup · rs1383994228 · VCV1924235

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00284%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -2.7, phastCons 0.4
Overall
CADD	19.63	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00284% East Asian · 1/35,210 alleles

Overall 0.00014% 2/1,428,844 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00284%	35,210
European (non-Finnish)	9.15e-05%	1,092,562

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: ATRIP
Protein: p.Ser31fs
Coding: c.89dup
MANE Select: NM_130384
dbSNP: rs1383994228
Type: Duplication
Location: chr3:48446928 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 31: the 'disordered' region

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

Similar variants

ATRIP p.Ser31Arg Uncertain significance ★★ ⚠ same residue
TREX1 p.Val31Ile Uncertain significance ★★ ⚠ same residue
ATRIP p.Ser31Asn Uncertain significance ★ ⚠ same residue
ATRIP p.Ser31Ile Uncertain significance ★ ⚠ same residue
TREX1 p.Asp200dup Likely pathogenic ★★ same type
TREX1 p.Cys42Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Cys99fs Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Cys99Ter Pathogenic/Likely pathogenic ★★ 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/atrip-p-ser31fs (accessed [today's date]).

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