Is TULP1 p.Tyr321Asp (c.961T>G) pathogenic?

TULP1 p.Tyr321Asp (c.961T>G) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-06-14). AlphaMissense: likely pathogenic (0.9913); Very rare (popmax 0.00133%, afr); Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Tyr321Asp (c.961T>G)?

TULP1 p.Tyr321Asp (c.961T>G) is associated with TULP1-related disorder, retinitis pigmentosa 14, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Tyr321Asp (c.961T>G) in the general population?

TULP1 p.Tyr321Asp (c.961T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Tyr321Asp (c.961T>G)?

AlphaMissense predicts likely pathogenic (score 0.9913) — an in-silico prediction, not a clinical call.

TULP1 p.Tyr321Asp

c.961T>G · rs794726991 · VCV193654

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TULP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9913	likely pathogenic · top 6% in TULP1
REVEL	0.978	strongly pathogenic-leaning
SaProt	LLR -13.26	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 11	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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,052 alleles

Overall 0.000124% 2/1,613,944 alleles · very rare exomes 2/1,461,618 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,052
European (non-Finnish)	8.47e-05%	1,180,032

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.Tyr321Asp
Coding: c.961T>G
MANE Select: NM_003322
dbSNP: rs794726991
Type: single nucleotide variant
Location: chr6:35506041 (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

Disease context

TULP1-related disorder

Also linked: retinitis pigmentosa 14 Leber congenital amaurosis 15

Similar variants

TULP1 p.Tyr321Ter Likely pathogenic ★ same residue
TULP1 p.Tyr321Cys Pathogenic ★ same residue
TULP1 p.Tyr321His Likely pathogenic ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same condition
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 c.99+1G>A Pathogenic/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/tulp1-p-tyr321asp (accessed [today's date]).

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