Is UPF1 p.Pro80= (c.240C>T) pathogenic?

UPF1 p.Pro80= (c.240C>T) is classified Likely benign in UPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Rare (popmax 0.356%, nfe).

How common is UPF1 p.Pro80= (c.240C>T) in the general population?

UPF1 p.Pro80= (c.240C>T) is rare (popmax 0.356%, nfe) (gnomAD).

UPF1 p.Pro80=

c.240C>T · rs35427308 · VCV2649593

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.356%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.4	GERP -2.8
Overall
CADD	2.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.356% European (non-Finnish) · 4,204/1,179,986 alleles

Filtering AF 0.347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.344%

Overall 0.305% 4,920/1,613,934 alleles · rare exomes 4,513/1,461,636 · genomes 407/152,298 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.432%	231
Finnishnot grpmax-eligible	0.417%	240
European (non-Finnish)grpmax	0.356%	281
Middle Eastern	0.346%	289
Remaining individualsnot grpmax-eligible	0.242%	414
Admixed American	0.177%	566
African / African-American	0.0453%	2,207
South Asian	0.011%	9,108

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: UPF1
Protein: p.Pro80=
Coding: c.240C>T
MANE Select: NM_002911
dbSNP: rs35427308
Type: single nucleotide variant
Location: chr19:18845988 (GRCh38)
Gene constraint: LOEUF 0.125 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.58 · 12 PDB
Residue 80: the 'sufficient for interaction with rent2' region

Full UPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UPF1 c.1266-32T>G Benign ★★ same type
UPF1 c.1544+108G>A Benign ★★ same type
UPF1 c.2300+75T>C Benign ★★ same type
UPF1 c.232-90G>A Benign ★★ same type
UPF1 c.2457+89G>A Benign ★★ same type
UPF1 c.2458-85G>T Benign ★★ same type
UPF1 c.2601-188G>C Benign ★★ same type
UPF1 c.2601-47A>G Benign ★★ 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/upf1-p-pro80 (accessed [today's date]).

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