Is DDHD2 p.Ser35fs (c.94_101dup) pathogenic?

DDHD2 p.Ser35fs (c.94101dup) is classified Pathogenic in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-19). Absent from gnomAD.

How common is DDHD2 p.Ser35fs (c.94_101dup) in the general population?

DDHD2 p.Ser35fs (c.94_101dup) is absent from gnomAD (gnomAD).

DDHD2 p.Ser35fs

c.94_101dup · rs1554510884 · VCV523988

Pathogenic Single submitter

Classification

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 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, 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: DDHD2
Protein: p.Ser35fs
Coding: c.94_101dup
MANE Select: NM_015214
dbSNP: rs1554510884
Type: Duplication
Location: chr8:38233086 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70
Residue 35: the wwe domain

Full DDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDHD2 p.Ser35Arg Uncertain significance ★ ⚠ same residue
DDHD2 p.Ser35Gly Uncertain significance ★ ⚠ same residue
DDHD2 c.1611_1617+4dup Likely pathogenic ★ same type
DDHD2 p.Asp631Ter Likely pathogenic ★ same type
DDHD2 p.Ile463fs Pathogenic ★ same type
DDHD2 c.1891+2dup Uncertain significance ★ same type
DDHD2 c.1057+9dup Benign ★ same type
DDHD2 c.1249-235dup 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/ddhd2-p-ser35fs (accessed [today's date]).

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