Is SEC24D p.Ser2fs (c.5dup) pathogenic?

SEC24D p.Ser2fs (c.5dup) is classified Likely pathogenic in SEC24D (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-06). No gnomAD frequency available for this variant.

How common is SEC24D p.Ser2fs (c.5dup) in the general population?

SEC24D p.Ser2fs (c.5dup) is no gnomAD frequency available for this variant (gnomAD).

SEC24D p.Ser2fs

c.5dup · rs1730973578 · VCV988445

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -3.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SEC24D
Protein: p.Ser2fs
Coding: c.5dup
MANE Select: NM_014822
dbSNP: rs1730973578
Type: Duplication
Location: chr4:118833691 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 6 PDB
Residue 2: the 'disordered' region

Full SEC24D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC24D c.1422-10_1422-9dup Benign/Likely benign ★★ same type
SEC24D c.1422-9dup Benign ★★ same type
SEC24D c.2959-15dup Benign/Likely benign ★★ same type
SEC24D p.Ile786fs Pathogenic ★ same type
SEC24D p.Pro10fs Likely pathogenic ★ same type
SEC24D p.Thr39fs Pathogenic ★ same type
SEC24D p.Thr51fs Pathogenic ★ same type
SEC24D p.Val7fs 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/sec24d-p-ser2fs (accessed [today's date]).

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