Is HID1 p.Val290= (c.870C>A) pathogenic?

HID1 p.Val290= (c.870C>A) is classified Likely benign in HID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0397%, nfe).

How common is HID1 p.Val290= (c.870C>A) in the general population?

HID1 p.Val290= (c.870C>A) is ultra-rare (popmax 0.0397%, nfe) (gnomAD).

HID1 p.Val290=

c.870C>A · rs139963690 · VCV2648249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0397%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 0.25, phastCons 1
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0397% European (non-Finnish) · 468/1,180,058 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0355%

Overall 0.0311% 502/1,613,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
European (non-Finnish)grpmax	0.0397%	2,521
Remaining individualsnot grpmax-eligible	0.0208%	4,806
Middle Eastern	0.0164%	6,084
Admixed American	0.0117%	8,573
South Asian	0.00988%	10,121
African / African-American	0.004%	24,983

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val290=
Coding: c.870C>A
MANE Select: NM_030630
dbSNP: rs139963690
Type: single nucleotide variant
Location: chr17:74960107 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13
Residue 290: 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-val290 (accessed [today's date]).

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