Is PIGB p.Arg339Trp (c.1015C>T) pathogenic?

PIGB p.Arg339Trp (c.1015C>T) is classified Uncertain significance in PIGB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-26). AlphaMissense: likely benign (0.1023); Ultra-rare (popmax 0.0269%, amr); Associated with Inborn genetic diseases.

What condition is associated with PIGB p.Arg339Trp (c.1015C>T)?

PIGB p.Arg339Trp (c.1015C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIGB p.Arg339Trp (c.1015C>T) in the general population?

PIGB p.Arg339Trp (c.1015C>T) is ultra-rare (popmax 0.0269%, amr) (gnomAD).

What do computational predictors say about PIGB p.Arg339Trp (c.1015C>T)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

PIGB p.Arg339Trp

c.1015C>T · rs777281224 · VCV2416415

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.014	GERP 0.27
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.4 · regional, not allelic
Overall
CADD	22.0	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 0.0269% Admixed American · 16/59,524 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00199% 32/1,610,264 alleles · ultra-rare exomes 24/1,458,200 · genomes 8/152,064 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0269%	3,720
African / African-American	0.0107%	9,359
Remaining individualsnot grpmax-eligible	0.0016%	62,368
European (non-Finnish)	0.000594%	168,290

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: PIGB
Protein: p.Arg339Trp
Coding: c.1015C>T
MANE Select: NM_004855
dbSNP: rs777281224
Type: single nucleotide variant
Location: chr15:55340780 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.48
Residue 339: a UniProt-annotated variant site (in dee80; uncertain significance)

Full PIGB 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

Similar variants

PIGB p.Arg339Gln Uncertain significance ★ ⚠ same residue
PIGB p.Arg339= Likely benign ★ same residue
PIGB p.Ala400Thr Uncertain significance ★★ ⚠ same condition
PIGB p.Asn482Lys Uncertain significance ★★ ⚠ same condition
PIGB p.Cys180Ser Uncertain significance ★★ ⚠ same condition
PIGB p.Gln419Arg Uncertain significance ★★ ⚠ same condition
PIGB p.Glu359Lys Uncertain significance ★★ ⚠ same condition
PIGB p.Gly102Ser Uncertain significance ★★ 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/pigb-p-arg339trp (accessed [today's date]).

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