Is TCERG1 p.Pro407Ser (c.1219C>T) pathogenic?

TCERG1 p.Pro407Ser (c.1219C>T) is classified Uncertain significance in TCERG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.7205); Very rare (popmax 0.00673%, afr).

How common is TCERG1 p.Pro407Ser (c.1219C>T) in the general population?

TCERG1 p.Pro407Ser (c.1219C>T) is very rare (popmax 0.00673%, afr) (gnomAD).

What do computational predictors say about TCERG1 p.Pro407Ser (c.1219C>T)?

AlphaMissense predicts likely pathogenic (score 0.7205) — an in-silico prediction, not a clinical call.

TCERG1 p.Pro407Ser

c.1219C>T · VCV3966413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7205	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 40 kb · p 2.1e-09 · regional, not allelic
Overall
CADD	24.0	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 0.00673% African / African-American · 5/74,306 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00163%

Overall 0.000375% 6/1,601,242 alleles · very rare exomes 4/1,449,122 · genomes 2/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00673%	14,861
Remaining individualsnot grpmax-eligible	0.00162%	61,894

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: TCERG1
Protein: p.Pro407Ser
Coding: c.1219C>T
MANE Select: NM_001382548
Type: single nucleotide variant
Location: chr5:146469564 (GRCh38)
Gene constraint: LOEUF 0.323 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.35 · 29 PDB

Full TCERG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TCERG1 p.Ala189Val Uncertain significance ★ ⚠ same type
TCERG1 p.Ala191Ser Uncertain significance ★ ⚠ same type
TCERG1 p.Ala195Val Uncertain significance ★ ⚠ same type
TCERG1 p.Ala205Val Uncertain significance ★ ⚠ same type
TCERG1 p.Ala245Val Uncertain significance ★ ⚠ same type
TCERG1 p.Ala253Val Uncertain significance ★ ⚠ same type
TCERG1 p.Ala424Ser Uncertain significance ★ ⚠ same type
TCERG1 p.Ala429Val 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/tcerg1-p-pro407ser (accessed [today's date]).

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