Is AFP p.Gln463= (c.1389A>G) pathogenic?

AFP p.Gln463= (c.1389A>G) is classified Likely benign in AFP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Ultra-rare (popmax 0.06%, amr).

How common is AFP p.Gln463= (c.1389A>G) in the general population?

AFP p.Gln463= (c.1389A>G) is ultra-rare (popmax 0.06%, amr) (gnomAD).

AFP p.Gln463=

c.1389A>G · rs145185829 · VCV733977

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, amr)

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 -0.63	GERP -3.7
Overall
CADD	1.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.06% Admixed American · 36/59,998 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.0228% 368/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.06%	1,667
European (non-Finnish)	0.0265%	3,770
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Middle Eastern	0.0164%	6,080
African / African-American	0.00667%	14,984

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: AFP
Protein: p.Gln463=
Coding: c.1389A>G
MANE Select: NM_001134
dbSNP: rs145185829
Type: single nucleotide variant
Location: chr4:73450714 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83 · 5 PDB
Residue 463: a disulfide bond; the albumin 3 domain; a β-strand

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

Similar variants

AFP c.714-5C>T Likely benign ★★ same type
AFP p.Ser286= Benign ★★ same type
AFP p.Ser445= Benign ★★ same type
AFP p.Gly608Arg Likely pathogenic ★ ⚠ same type
AFP p.Ala134Val Uncertain significance ★ ⚠ same type
AFP p.Ala471Val Uncertain significance ★ ⚠ same type
AFP p.Ala476Thr Uncertain significance ★ ⚠ same type
AFP p.Ala476Val 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/afp-p-gln463 (accessed [today's date]).

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