Is PFAS p.Pro736Ala (c.2206C>G) pathogenic?

PFAS p.Pro736Ala (c.2206C>G) is classified Uncertain significance in PFAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.0793); Absent from gnomAD v4.1.

How common is PFAS p.Pro736Ala (c.2206C>G) in the general population?

PFAS p.Pro736Ala (c.2206C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PFAS p.Pro736Ala (c.2206C>G)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

PFAS p.Pro736Ala

c.2206C>G · rs2543833408 · VCV3211537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.51, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,370 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	17.2	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.Pro736Ala
Coding: c.2206C>G
MANE Select: NM_012393
dbSNP: rs2543833408
Type: single nucleotide variant
Location: chr17:8265051 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 3 PDB

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

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-pro736ala (accessed [today's date]).

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