Is TADA2A p.Phe40Ser (c.119T>C) pathogenic?

TADA2A p.Phe40Ser (c.119T>C) is classified Uncertain significance in TADA2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1941); Very rare (popmax 0.000254%, nfe).

How common is TADA2A p.Phe40Ser (c.119T>C) in the general population?

TADA2A p.Phe40Ser (c.119T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about TADA2A p.Phe40Ser (c.119T>C)?

AlphaMissense predicts likely benign (score 0.1941) — an in-silico prediction, not a clinical call.

TADA2A p.Phe40Ser

c.119T>C · VCV4179461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1941	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -3.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 63 kb · p 0.014 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000254% European (non-Finnish) · 3/1,179,592 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,454 alleles · very rare exomes 3/1,460,194 · genomes 0/152,260 · 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: TADA2A
Protein: p.Phe40Ser
Coding: c.119T>C
MANE Select: NM_001166105
Type: single nucleotide variant
Location: chr17:37423602 (GRCh38)
Gene constraint: LOEUF 0.657 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.04 · 1 PDB

Full TADA2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADA2 c.754-2A>G Likely pathogenic ★★ same type
ADA2 c.882-2A>G Pathogenic ★★ same type
ADA2 c.973-2A>G Pathogenic ★★ same type
ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same type
ADA2 p.Arg169Trp Pathogenic/Likely pathogenic ★★ same type
ADA2 p.Arg306Ter Likely pathogenic ★★ same type
ADA2 p.Arg312Ter Pathogenic ★★ same type
ADA2 p.Asn370Lys 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/tada2a-p-phe40ser (accessed [today's date]).

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