Is HID1 p.Ser430Arg (c.1290C>A) pathogenic?

HID1 p.Ser430Arg (c.1290C>A) is classified Uncertain significance in HID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is HID1 p.Ser430Arg (c.1290C>A) in the general population?

HID1 p.Ser430Arg (c.1290C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HID1 p.Ser430Arg (c.1290C>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

HID1 p.Ser430Arg

c.1290C>A · VCV3857801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,178)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 1% in HID1
REVEL	0.589	indeterminate
SaProt	LLR -16.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3.1	GERP -3
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 9e-09 · regional, not allelic
Overall
CADD	19.34	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,603,178). 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: HID1
Protein: p.Ser430Arg
Coding: c.1290C>A
MANE Select: NM_030630
Type: single nucleotide variant
Location: chr17:74958429 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13
Residue 430: a UniProt-annotated variant site (in dee105; likely pathogenic)

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

Similar variants

HID1 p.Asp201Asn Uncertain significance ★★ same type
HID1 p.Ser87Leu Uncertain significance ★★ ⚠ same type
DMC1 p.Met200Val Benign ★★ ⚠ same type
HID1 c.1149+7C>T Benign ★★ same type
HID1 p.Gln130Glu Benign ★★ same type
HID1 p.His192Tyr Benign ★★ same type
HID1 c.1149+1G>T Likely pathogenic ★ same type
HID1 p.Arg668Ter 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/hid1-p-ser430arg (accessed [today's date]).

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