Is TDRD7 p.Arg751= (c.2251A>C) pathogenic?

TDRD7 p.Arg751= (c.2251A>C) is classified Uncertain significance in TDRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0267%, amr); Associated with cataract 36.

What condition is associated with TDRD7 p.Arg751= (c.2251A>C)?

TDRD7 p.Arg751= (c.2251A>C) is associated with cataract 36 (ClinVar).

How common is TDRD7 p.Arg751= (c.2251A>C) in the general population?

TDRD7 p.Arg751= (c.2251A>C) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

TDRD7 p.Arg751=

c.2251A>C · rs1171168935 · VCV913766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

cataract 36

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 5.9	GERP 0.12, phastCons 1
Overall
CADD	9.722	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/59,996 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00118% 19/1,613,968 alleles · ultra-rare exomes 10/1,461,780 · genomes 9/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000169%	589,991

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: TDRD7
Protein: p.Arg751=
Coding: c.2251A>C
MANE Select: NM_014290
dbSNP: rs1171168935
Type: single nucleotide variant
Location: chr9:97478523 (GRCh38)
Gene constraint: LOEUF 0.521 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 73.60 · 1 PDB
Residue 751: the tudor 2 domain

Full TDRD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 36 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TDRD7 p.Ala651Thr Uncertain significance ★★ ⚠ same condition
TDRD7 p.Ala895Thr Uncertain significance ★★ ⚠ same condition
TDRD7 p.Ala958Thr Uncertain significance ★★ ⚠ same condition
TDRD7 p.Arg1013Gln Uncertain significance ★★ ⚠ same condition
TDRD7 p.Arg99Cys Uncertain significance ★★ ⚠ same condition
TDRD7 p.Asn631Ser Uncertain significance ★★ ⚠ same condition
TDRD7 p.Glu63Asp Uncertain significance ★★ ⚠ same condition
TDRD7 p.His421Asn 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/tdrd7-p-arg751 (accessed [today's date]).

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