Is TULP1 p.Asp355His (c.1063G>C) pathogenic?

TULP1 p.Asp355His (c.1063G>C) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). AlphaMissense: likely pathogenic (0.8882); Very rare (popmax 0.000424%, nfe).

How common is TULP1 p.Asp355His (c.1063G>C) in the general population?

TULP1 p.Asp355His (c.1063G>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about TULP1 p.Asp355His (c.1063G>C)?

AlphaMissense predicts likely pathogenic (score 0.8882) — an in-silico prediction, not a clinical call.

TULP1 p.Asp355His

c.1063G>C · rs1085307806 · VCV2763586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8882	likely pathogenic
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,016 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,082 alleles · very rare exomes 5/1,461,888 · genomes 0/152,194 · joint denominator

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: TULP1
Protein: p.Asp355His
Coding: c.1063G>C
MANE Select: NM_003322
dbSNP: rs1085307806
Type: single nucleotide variant
Location: chr6:35505790 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TULP1 p.Asp355Val Uncertain significance ★★ ⚠ same residue
TULP1 p.Asp355Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same type
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.718+2T>C Pathogenic ★★ same type
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.999+5G>C Pathogenic/Likely 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/tulp1-p-asp355his (accessed [today's date]).

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