Is APBB1 p.Arg51Cys (c.151C>T) pathogenic?

APBB1 p.Arg51Cys (c.151C>T) is classified Benign in APBB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-10). AlphaMissense: likely benign (0.14); Low-frequency (popmax 4.76%, amr).

How common is APBB1 p.Arg51Cys (c.151C>T) in the general population?

APBB1 p.Arg51Cys (c.151C>T) is low-frequency (popmax 4.76%, amr) (gnomAD).

What do computational predictors say about APBB1 p.Arg51Cys (c.151C>T)?

AlphaMissense predicts likely benign (score 0.14) — an in-silico prediction, not a clinical call.

APBB1 p.Arg51Cys

c.151C>T · rs141737231 · VCV771439

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.14 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.76%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.14	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 15 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.5	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 4.76% Admixed American · 2,855/59,940 alleles

Filtering AF 4.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.56%

Overall 0.246% 3,961/1,607,808 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.76%	21
Remaining individualsnot grpmax-eligible	0.248%	403
European (non-Finnish)	0.074%	1,352
African / African-American	0.0666%	1,501
Finnishnot grpmax-eligible	0.0372%	2,691
Middle Eastern	0.0165%	6,052
East Asian	0.00446%	22,418
South Asian	0.0044%	22,741

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: APBB1
Protein: p.Arg51Cys
Coding: c.151C>T
MANE Select: NM_001164
dbSNP: rs141737231
Type: single nucleotide variant
Location: chr11:6411197 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.75 · 11 PDB

Full APBB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB1 p.Arg51His Uncertain significance ★ ⚠ same residue
SMPD1 p.Arg498Leu Pathogenic ★★ same type
APBB1 p.Ala371= Benign ★★ same type
APBB1 p.Asn126= Benign ★★ same type
APBB1 p.Leu385= Benign ★★ same type
APBB1 p.Met327Val Likely benign ★★ same type
APBB1 c.721+1G>T Uncertain significance ★ same type
APBB1 p.Ala157Val 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/apbb1-p-arg51cys (accessed [today's date]).

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