Is HID1 p.Asp201Asn (c.601G>A) pathogenic?

HID1 p.Asp201Asn (c.601G>A) is classified Uncertain significance in HID1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-30). AlphaMissense: ambiguous (0.527); Ultra-rare (popmax 0.0707%, afr); Associated with developmental and epileptic encephalopathy 105 with hypopituitarism.

What condition is associated with HID1 p.Asp201Asn (c.601G>A)?

HID1 p.Asp201Asn (c.601G>A) is associated with developmental and epileptic encephalopathy 105 with hypopituitarism (ClinVar).

How common is HID1 p.Asp201Asn (c.601G>A) in the general population?

HID1 p.Asp201Asn (c.601G>A) is ultra-rare (popmax 0.0707%, afr) (gnomAD).

What do computational predictors say about HID1 p.Asp201Asn (c.601G>A)?

AlphaMissense predicts ambiguous (score 0.527) — an in-silico prediction, not a clinical call.

HID1 p.Asp201Asn

c.601G>A · VCV3582826

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, afr)

Conditions

developmental and epileptic encephalopathy 105 with hypopituitarism

Computational evidence

Protein change
AlphaMissense	0.527	ambiguous
REVEL	0.399	indeterminate
SaProt	LLR -13.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 9e-09 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0707% African / African-American · 53/74,952 alleles

Filtering AF 0.0555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0501%

Overall 0.00765% 123/1,607,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0707%	1,414
Remaining individualsnot grpmax-eligible	0.0161%	6,219
East Asian	0.0112%	8,930
Finnishnot grpmax-eligible	0.00783%	12,778
South Asian	0.00772%	12,961
Admixed American	0.0067%	14,927
European (non-Finnish)	0.00332%	30,127

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.Asp201Asn
Coding: c.601G>A
MANE Select: NM_030630
Type: single nucleotide variant
Location: chr17:74962244 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13
Residue 201: a UniProt-annotated variant site (in dee105; likely pathogenic)

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.Asp201Tyr Uncertain significance ★ ⚠ same residue
HID1 c.1392+5G>C Uncertain significance ★ same condition
HID1 p.Asp719Glu Uncertain significance ★ ⚠ same condition
HID1 p.Thr121= Uncertain significance ★ same condition
HID1 p.Arg433Trp Pathogenic same condition
HID1 p.Gly187Asp Pathogenic same condition
HID1 p.Ala754fs Likely pathogenic ★ same condition
HID1 p.Ser660fs 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-asp201asn (accessed [today's date]).

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