Is HID1 p.Val774fs (c.2318dup) pathogenic?

HID1 p.Val774fs (c.2318dup) is classified Pathogenic in HID1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-10). Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy 105 with hypopituitarism.

What condition is associated with HID1 p.Val774fs (c.2318dup)?

HID1 p.Val774fs (c.2318dup) is associated with developmental and epileptic encephalopathy 105 with hypopituitarism (ClinVar).

How common is HID1 p.Val774fs (c.2318dup) in the general population?

HID1 p.Val774fs (c.2318dup) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

HID1 p.Val774fs

c.2318dup · rs2039300041 · VCV1700642

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

developmental and epileptic encephalopathy 105 with hypopituitarism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (19 of 19) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.93	GERP -2.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,532 alleles

Overall 6.85e-05% 1/1,460,486 alleles · very rare

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: HID1
Protein: p.Val774fs
Coding: c.2318dup
MANE Select: NM_030630
dbSNP: rs2039300041
Type: Duplication
Location: chr17:74951618 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13
Residue 774: a UniProt-annotated variant site (in dee105; likely pathogenic); the 'required for protein function' region

Full HID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy 105 with hypopituitarism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HID1 p.Asp201Asn Uncertain significance ★★ same condition
HID1 p.Ala754fs Likely pathogenic ★ same condition
HID1 p.Ser660fs Pathogenic ★ same condition
HID1 c.1392+5G>C Uncertain significance ★ same condition
HID1 p.Arg758fs Uncertain significance ★ same condition
HID1 p.Asp719Glu Uncertain significance ★ ⚠ same condition
HID1 p.Thr121= Uncertain significance ★ same condition
HID1 p.Arg433Trp Pathogenic same condition

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/hid1-p-val774fs (accessed [today's date]).

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