Is AFP p.Phe50Tyr (c.149T>A) pathogenic?

AFP p.Phe50Tyr (c.149T>A) is classified Likely benign in AFP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-09). AlphaMissense: likely benign (0.1502); Rare (popmax 0.319%, afr); Associated with AFP-related disorder.

What condition is associated with AFP p.Phe50Tyr (c.149T>A)?

AFP p.Phe50Tyr (c.149T>A) is associated with AFP-related disorder (ClinVar).

How common is AFP p.Phe50Tyr (c.149T>A) in the general population?

AFP p.Phe50Tyr (c.149T>A) is rare (popmax 0.319%, afr) (gnomAD).

What do computational predictors say about AFP p.Phe50Tyr (c.149T>A)?

AlphaMissense predicts likely benign (score 0.1502) — an in-silico prediction, not a clinical call.

AFP p.Phe50Tyr

c.149T>A · rs146576905 · VCV3051185

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1502 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.319%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AFP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1502	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.54	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 0.95	GERP -2.1, phastCons 0.95
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	19.87	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 0.319% African / African-American · 239/75,010 alleles

Filtering AF 0.285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.273%

Overall 0.0174% 280/1,613,388 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.319%	314
Admixed American	0.045%	2,222
Remaining individualsnot grpmax-eligible	0.0224%	4,463

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.Phe50Tyr
Coding: c.149T>A
MANE Select: NM_001134
dbSNP: rs146576905
Type: single nucleotide variant
Location: chr4:73438185 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.83 · 5 PDB
Residue 50: the albumin 1 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.Cys511= Likely benign same condition
AFP p.Gly482= 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-phe50tyr (accessed [today's date]).

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