Is SUFU p.Thr196Pro (c.586A>C) pathogenic?

SUFU p.Thr196Pro (c.586A>C) is classified Uncertain significance in SUFU (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-22). AlphaMissense: ambiguous (0.4595); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SUFU p.Thr196Pro (c.586A>C)?

SUFU p.Thr196Pro (c.586A>C) is associated with hereditary neoplastic syndrome, nevoid basal cell carcinoma syndrome, medulloblastoma (ClinVar).

How common is SUFU p.Thr196Pro (c.586A>C) in the general population?

SUFU p.Thr196Pro (c.586A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUFU p.Thr196Pro (c.586A>C)?

AlphaMissense predicts ambiguous (score 0.4595) — an in-silico prediction, not a clinical call.

SUFU p.Thr196Pro

c.586A>C · rs2135867363 · VCV1398943

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4595 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4595	ambiguous
REVEL	0.522	indeterminate
SaProt	LLR -10.64	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -0.56, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 126 kb · p 5.7e-14 · regional, not allelic
Overall
CADD	21.4	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: SUFU
Protein: p.Thr196Pro
Coding: c.586A>C
MANE Select: NM_016169
dbSNP: rs2135867363
Type: single nucleotide variant
Location: chr10:102592713 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 10 PDB
Residue 196: a β-strand

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

Also linked: nevoid basal cell carcinoma syndrome medulloblastoma

Similar variants

SUFU p.Thr196Ile Uncertain significance ★★ ⚠ same residue
SUFU p.Thr196= Likely benign ★★ same residue
SUFU p.Thr196Ala Uncertain significance ★ ⚠ same residue
SUFU p.Thr196Ser Uncertain significance ★ ⚠ same residue
SUFU p.Thr196fs Pathogenic ★★ same residue
SUFU c.1022+1G>A Pathogenic ★★ same condition
SUFU c.1023-2A>T Likely pathogenic ★★ same condition
SUFU c.683+1G>A Likely pathogenic ★★ 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-thr196pro (accessed [today's date]).

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