Is SUFU p.Pro49= (c.147G>T) pathogenic?

SUFU p.Pro49= (c.147G>T) is classified Likely benign in SUFU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with SUFU p.Pro49= (c.147G>T)?

SUFU p.Pro49= (c.147G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SUFU p.Pro49= (c.147G>T) in the general population?

SUFU p.Pro49= (c.147G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

SUFU p.Pro49=

c.147G>T · VCV4177530

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

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 1.1	GERP -3.2, phastCons 1
Overall
CADD	11.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,964 alleles

Overall 0.000124% 2/1,609,684 alleles · very rare exomes 2/1,457,900 · genomes 0/151,784 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,964
European (non-Finnish)	8.49e-05%	1,177,544

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: SUFU
Protein: p.Pro49=
Coding: c.147G>T
MANE Select: NM_016169
Type: single nucleotide variant
Location: chr10:102504299 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SUFU p.Pro49Leu Uncertain significance ★★ ⚠ same residue
SUFU p.Pro49Arg Uncertain significance ★ same residue
SUFU p.Pro49Ala Uncertain significance ★ ⚠ same residue
SUFU c.1022+1G>A Pathogenic ★★ same condition
SUFU p.Arg146Ter Pathogenic ★★ same condition
SUFU p.Arg299Ter Pathogenic ★★ same condition
SUFU p.Trp88Ter Pathogenic/Likely pathogenic ★★ same condition
SUFU c.1158-3C>T Uncertain significance ★★ same condition

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/sufu-p-pro49 (accessed [today's date]).

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