Is APBB1 p.Met327Val (c.979A>G) pathogenic?

APBB1 p.Met327Val (c.979A>G) is classified Likely benign in APBB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0539); Rare (popmax 0.926%, nfe).

How common is APBB1 p.Met327Val (c.979A>G) in the general population?

APBB1 p.Met327Val (c.979A>G) is rare (popmax 0.926%, nfe) (gnomAD).

What do computational predictors say about APBB1 p.Met327Val (c.979A>G)?

AlphaMissense predicts likely benign (score 0.0539) — an in-silico prediction, not a clinical call.

APBB1 p.Met327Val

c.979A>G · rs1800423 · VCV720166

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0539 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.926%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0539	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.21	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 2.3	GERP -0.47, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 15 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	18.02	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 0.926% European (non-Finnish) · 10,927/1,179,978 alleles

Filtering AF 0.911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.905%

Overall 0.769% 12,413/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.16%	87
European (non-Finnish)grpmax	0.926%	108
Middle Eastern	0.742%	135
Remaining individualsnot grpmax-eligible	0.715%	140
Admixed American	0.412%	243
South Asian	0.217%	460
African / African-American	0.168%	596
Finnishnot grpmax-eligible	0.106%	942
East Asian	0.029%	3,452

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met327Val
Coding: c.979A>G
MANE Select: NM_001164
dbSNP: rs1800423
Type: single nucleotide variant
Location: chr11:6403380 (GRCh38)
Gene constraint: LOEUF 0.401 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.75 · 11 PDB
Residue 327: a UniProt-annotated variant site (in)

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

Similar variants

SMPD1 p.Arg498Leu Pathogenic ★★ same type
APBB1 p.Ala371= Benign ★★ same type
APBB1 p.Arg51Cys Benign ★★ same type
APBB1 p.Asn126= Benign ★★ same type
APBB1 p.Leu385= Benign ★★ same type
APBB1 c.721+1G>T Uncertain significance ★ same type
APBB1 p.Ala157Val Uncertain significance ★ ⚠ same type
APBB1 p.Ala194Asp 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-met327val (accessed [today's date]).

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