Is TDRD7 p.Ser623= (c.1869A>G) pathogenic?

TDRD7 p.Ser623= (c.1869A>G) is classified Benign/Likely benign in TDRD7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-05). Low-frequency (popmax 2.77%, afr); Associated with cataract 36.

What condition is associated with TDRD7 p.Ser623= (c.1869A>G)?

TDRD7 p.Ser623= (c.1869A>G) is associated with cataract 36 (ClinVar).

How common is TDRD7 p.Ser623= (c.1869A>G) in the general population?

TDRD7 p.Ser623= (c.1869A>G) is low-frequency (popmax 2.77%, afr) (gnomAD).

TDRD7 p.Ser623=

c.1869A>G · rs115297535 · VCV364070

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.77%, afr)

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 0.53	GERP -5, phastCons 0.85
Overall
CADD	5.925	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.77% African / African-American · 2,075/75,030 alleles

Filtering AF 2.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.63%

Overall 0.151% 2,435/1,613,968 alleles · low-frequency exomes 1,198/1,461,686 · genomes 1,237/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.77%	36
Admixed American	0.272%	368
Remaining individualsnot grpmax-eligible	0.237%	422
Middle Eastern	0.116%	865
South Asian	0.0143%	7,006
European (non-Finnish)	0.00246%	40,686

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.Ser623=
Coding: c.1869A>G
MANE Select: NM_014290
dbSNP: rs115297535
Type: single nucleotide variant
Location: chr9:97472420 (GRCh38)
Gene constraint: LOEUF 0.521 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 73.60 · 1 PDB

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-ser623 (accessed [today's date]).

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