Is PFAS p.Asp685= (c.2055C>T) pathogenic?

PFAS p.Asp685= (c.2055C>T) is classified Likely benign in PFAS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-23). Ultra-rare (popmax 0.0271%, amr).

How common is PFAS p.Asp685= (c.2055C>T) in the general population?

PFAS p.Asp685= (c.2055C>T) is ultra-rare (popmax 0.0271%, amr) (gnomAD).

PFAS p.Asp685=

c.2055C>T · rs750037801 · VCV738301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0271%, 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 2.8	GERP -0.51, phastCons 1
Overall
CADD	9.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0271% Admixed American · 15/55,266 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00216% 34/1,573,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0271%	3,684
European (non-Finnish)	0.00164%	60,821

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: PFAS
Protein: p.Asp685=
Coding: c.2055C>T
MANE Select: NM_012393
dbSNP: rs750037801
Type: single nucleotide variant
Location: chr17:8264900 (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-asp685 (accessed [today's date]).

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