Is HDHD5 p.Arg152= (c.456A>G) pathogenic?

HDHD5 p.Arg152= (c.456A>G) is classified Likely benign in HDHD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Very rare (popmax 0.00839%, nfe).

How common is HDHD5 p.Arg152= (c.456A>G) in the general population?

HDHD5 p.Arg152= (c.456A>G) is very rare (popmax 0.00839%, nfe) (gnomAD).

HDHD5 p.Arg152=

c.456A>G · rs369297006 · VCV736647

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00839%, 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 1.5	GERP -2, phastCons 0.78
Overall
CADD	8.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00839% European (non-Finnish) · 99/1,179,990 alleles

Filtering AF 0.00702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00644% 104/1,613,824 alleles · very rare exomes 99/1,461,856 · genomes 5/151,968 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00839%	11,919
Remaining individualsnot grpmax-eligible	0.0048%	20,828
African / African-American	0.00267%	37,431

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: HDHD5
Protein: p.Arg152=
Coding: c.456A>G
MANE Select: NM_033070
dbSNP: rs369297006
Type: single nucleotide variant
Location: chr22:17145105 (GRCh38)
Gene constraint: LOEUF 1.287 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.64

Full HDHD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HDHD5 p.Arg152Gln Likely benign ★ same residue
HDHD5 p.Arg369Ser Benign ★★ same type
HDHD5 p.Arg416Cys Likely benign ★★ same type
HDHD5 p.Ala223Thr Uncertain significance ★ ⚠ same type
HDHD5 p.Ala24Pro Uncertain significance ★ ⚠ same type
HDHD5 p.Ala25Val Uncertain significance ★ ⚠ same type
HDHD5 p.Ala2Thr Uncertain significance ★ ⚠ same type
HDHD5 p.Ala2Val Uncertain significance ★ ⚠ 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/hdhd5-p-arg152 (accessed [today's date]).

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