Is PHKB p.Arg614His (c.1841G>A) pathogenic?

PHKB p.Arg614His (c.1841G>A) is classified Uncertain significance in PHKB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-28). AlphaMissense: likely benign (0.1768); Very rare (popmax 0.00936%, afr); Associated with Inborn genetic diseases.

What condition is associated with PHKB p.Arg614His (c.1841G>A)?

PHKB p.Arg614His (c.1841G>A) is associated with Inborn genetic diseases, glycogen storage disease IXb (ClinVar).

How common is PHKB p.Arg614His (c.1841G>A) in the general population?

PHKB p.Arg614His (c.1841G>A) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about PHKB p.Arg614His (c.1841G>A)?

AlphaMissense predicts likely benign (score 0.1768) — an in-silico prediction, not a clinical call.

PHKB p.Arg614His

c.1841G>A · rs140190371 · VCV2072667

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1768	likely benign
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -10.09	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00936% African / African-American · 7/74,802 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00341% 55/1,610,926 alleles · very rare exomes 49/1,458,858 · genomes 6/152,068 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,686
Remaining individualsnot grpmax-eligible	0.00641%	15,599
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,584
European (non-Finnish)	0.00331%	30,188
South Asian	0.0033%	30,332
East Asian	0.00223%	44,842

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: PHKB
Protein: p.Arg614His
Coding: c.1841G>A
MANE Select: NM_000293
dbSNP: rs140190371
Type: single nucleotide variant
Location: chr16:47650587 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease IXb

Similar variants

PHKB p.Arg614Cys Uncertain significance ★ ⚠ same residue
PHKB p.Arg614Ser Uncertain significance ★ ⚠ same residue
PHKB c.1127-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.1364-2A>G Pathogenic ★★ same condition
PHKB c.1972-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2427+965A>C Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2896-1G>T Pathogenic ★★ same condition
PHKB c.306-2A>G Pathogenic/Likely pathogenic ★★ same condition

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/phkb-p-arg614his (accessed [today's date]).

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