Is AFP p.Cys511= (c.1533C>T) pathogenic?

AFP p.Cys511= (c.1533C>T) is classified Likely benign in AFP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-23). Ultra-rare (popmax 0.031%, nfe); Associated with AFP-related disorder.

What condition is associated with AFP p.Cys511= (c.1533C>T)?

AFP p.Cys511= (c.1533C>T) is associated with AFP-related disorder (ClinVar).

How common is AFP p.Cys511= (c.1533C>T) in the general population?

AFP p.Cys511= (c.1533C>T) is ultra-rare (popmax 0.031%, nfe) (gnomAD).

AFP p.Cys511=

c.1533C>T · rs200600473 · VCV3040398

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.031%, nfe)

Conditions

AFP-related disorder

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 0.37	GERP 1.9, phastCons 0.99
Overall
CADD	7.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.031% European (non-Finnish) · 366/1,179,990 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0234% 377/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.031%	3,224
Remaining individualsnot grpmax-eligible	0.008%	12,497
Finnishnot grpmax-eligible	0.00625%	16,008
African / African-American	0.00267%	37,460

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.Cys511=
Coding: c.1533C>T
MANE Select: NM_001134
dbSNP: rs200600473
Type: single nucleotide variant
Location: chr4:73452505 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83 · 5 PDB
Residue 511: a disulfide bond; the albumin 3 domain; an α-helix

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

Disease context

AFP-related disorder

Similar variants

AFP c.844-10T>C Benign same condition
AFP p.Gly482= Likely benign same condition
AFP p.Phe50Tyr Likely benign same condition
AFP p.Thr547Ile Benign same condition
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

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-cys511 (accessed [today's date]).

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