Is HID1 p.Val488Met (c.1462G>A) pathogenic?

HID1 p.Val488Met (c.1462G>A) is classified Uncertain significance in HID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.1532); Very rare (popmax 0.00267%, afr).

How common is HID1 p.Val488Met (c.1462G>A) in the general population?

HID1 p.Val488Met (c.1462G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about HID1 p.Val488Met (c.1462G>A)?

AlphaMissense predicts likely benign (score 0.1532) — an in-silico prediction, not a clinical call.

HID1 p.Val488Met

c.1462G>A · rs781471632 · VCV3105798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1532	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 9e-09 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00267% African / African-American · 2/74,800 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000435% 7/1,608,208 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,400
Admixed American	0.00168%	59,368
South Asian	0.00111%	89,894
European (non-Finnish)	0.000255%	392,623

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.Val488Met
Coding: c.1462G>A
MANE Select: NM_030630
dbSNP: rs781471632
Type: single nucleotide variant
Location: chr17:74958150 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13
Residue 488: 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-val488met (accessed [today's date]).

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