Is TEC p.Arg202Ser (c.606A>C) pathogenic?

TEC p.Arg202Ser (c.606A>C) is classified Uncertain significance in TEC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: ambiguous (0.4166); Very rare (popmax 8.48e-05%, nfe).

How common is TEC p.Arg202Ser (c.606A>C) in the general population?

TEC p.Arg202Ser (c.606A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about TEC p.Arg202Ser (c.606A>C)?

AlphaMissense predicts ambiguous (score 0.4166) — an in-silico prediction, not a clinical call.

TEC p.Arg202Ser

c.606A>C · rs746270033 · VCV2330871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4166	ambiguous
REVEL	0.17	moderately benign-leaning
SaProt	LLR -10.09	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.87	GERP -0.59, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 79 kb · p 0.38 · regional, not allelic
Overall
CADD	21.4	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 8.48e-05% European (non-Finnish) · 1/1,179,902 alleles

Overall 6.2e-05% 1/1,613,948 alleles · very rare exomes 1/1,461,706 · genomes 0/152,242 · 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: TEC
Protein: p.Arg202Ser
Coding: c.606A>C
MANE Select: NM_003215
dbSNP: rs746270033
Type: single nucleotide variant
Location: chr4:48167843 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 1 PDB
Residue 202: the sh3 domain

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

Similar variants

TEC c.496-1G>A Likely pathogenic ★ same type
TEC p.Ala500Val Uncertain significance ★ ⚠ same type
TEC p.Arg262Leu Uncertain significance ★ ⚠ same type
TEC p.Arg29Gly Uncertain significance ★ ⚠ same type
TEC p.Arg342Gln Uncertain significance ★ ⚠ same type
TEC p.Arg390Gln Uncertain significance ★ same type
TEC p.Arg617Cys Uncertain significance ★ ⚠ same type
TEC p.Asn112Ile Uncertain significance ★ ⚠ 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/tec-p-arg202ser (accessed [today's date]).

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