PFAS p.Phe574Ser
c.1721T>C · VCV3931009
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5091 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5091 | ambiguous |
|---|---|---|
| REVEL | 0.241 | benign-leaning |
| SaProt | LLR -10.38 | damaging |
| ⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 9,952 bp · p 0.57 · regional, not allelic |
| Overall | ||
| CADD | 23.3 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PFAS
- Protein
- p.Phe574Ser
- Coding
- c.1721T>C
- MANE Select
- NM_012393
- Type
- single nucleotide variant
- Location
- chr17:8263866 (GRCh38)
- Gene constraint
- LOEUF 0.777 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.52 · 3 PDB
Similar variants
- CTC1 p.Pro9Ser Uncertain significance ★★ ⚠ same type
- CTC1 p.Ser11= Uncertain significance ★★ same type
- CTC1 c.33+9T>C Likely benign ★★ same type
- PFAS p.Ala466Thr Benign ★★ same type
- PFAS p.Arg572Gln Likely benign ★★ same type
- PFAS p.Val661Met Likely benign ★★ same type
- CTC1 p.Met1Val Pathogenic ★ same type
- PFAS c.681-1G>A 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/pfas-p-phe574ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown