Is HMBS p.Arg164= (c.492G>A) pathogenic?

HMBS p.Arg164= (c.492G>A) is classified Likely benign in HMBS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-23). Absent from gnomAD v4.1.

How common is HMBS p.Arg164= (c.492G>A) in the general population?

HMBS p.Arg164= (c.492G>A) is absent from gnomAD v4.1 (gnomAD).

HMBS p.Arg164=

c.492G>A · VCV4798431

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 0.14, phastCons 1
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HMBS
Protein: p.Arg164=
Coding: c.492G>A
MANE Select: NM_000190
Type: single nucleotide variant
Location: chr11:119090259 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.54 · 11 PDB
Residue 164: a β-strand

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

Similar variants

HMBS p.Arg164Ser Uncertain significance ★★ same residue
HMBS p.Arg164Gly Uncertain significance ★ ⚠ same residue
HMBS p.Arg164delinsSerTer Pathogenic ★ same residue
HMBS p.Arg164del Uncertain significance ★ same residue
HMBS c.160+5G>C Pathogenic/Likely pathogenic ★★ same type
HMBS c.345-1G>A Pathogenic ★★ same type
HMBS c.613-1G>A Pathogenic ★★ same type
HMBS c.826-2A>T Pathogenic/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/hmbs-p-arg164 (accessed [today's date]).

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