Is PHB1 p.Asp152= (c.456C>T) pathogenic?

PHB1 p.Asp152= (c.456C>T) is classified Likely benign in PHB1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Ultra-rare (popmax 0.0134%, eas); Associated with PHB1-related disorder.

What condition is associated with PHB1 p.Asp152= (c.456C>T)?

PHB1 p.Asp152= (c.456C>T) is associated with PHB1-related disorder (ClinVar).

How common is PHB1 p.Asp152= (c.456C>T) in the general population?

PHB1 p.Asp152= (c.456C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

PHB1 p.Asp152=

c.456C>T · rs530616891 · VCV3047679

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

PHB1-related disorder

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 -0.16	GERP -3.7, phastCons 0.004
Overall
CADD	4.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,880 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000992% 16/1,613,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.0048%	20,822
African / African-American	0.00133%	75,016
South Asian	0.0011%	91,040
European (non-Finnish)	0.000424%	235,967

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: PHB1
Protein: p.Asp152=
Coding: c.456C>T
MANE Select: NM_002634
dbSNP: rs530616891
Type: single nucleotide variant
Location: chr17:49409096 (GRCh38)
Structure: AlphaFold pLDDT 89.36 · 6 PDB

Full PHB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHB1-related disorder

Similar variants

PHB1 c.393+9A>G Benign same condition
PHB1 c.511-12C>G Benign ★★ same type
PHB1 p.Leu251= Benign ★★ same type
PHB1 p.Ala244Val Uncertain significance ★ ⚠ same type
PHB1 p.Arg43Gly Uncertain significance ★ same type
PHB1 p.Arg72Gln Uncertain significance ★ ⚠ same type
PHB1 p.Arg93Cys Uncertain significance ★ ⚠ same type
PHB1 p.Asp68Tyr 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/phb1-p-asp152 (accessed [today's date]).

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