Is TCERG1 p.Ser347Pro (c.1039T>C) pathogenic?

TCERG1 p.Ser347Pro (c.1039T>C) is classified Uncertain significance in TCERG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.1276); Ultra-rare (popmax 0.0916%, amr).

How common is TCERG1 p.Ser347Pro (c.1039T>C) in the general population?

TCERG1 p.Ser347Pro (c.1039T>C) is ultra-rare (popmax 0.0916%, amr) (gnomAD).

What do computational predictors say about TCERG1 p.Ser347Pro (c.1039T>C)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

TCERG1 p.Ser347Pro

c.1039T>C · rs200378396 · VCV2359455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0916%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 4,631 bp · p 0.17 · regional, not allelic
Overall
CADD	23.3	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 0.0916% Admixed American · 55/60,022 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0653%

Overall 0.00477% 77/1,614,144 alleles · ultra-rare exomes 34/1,461,894 · genomes 43/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0916%	1,091
Remaining individualsnot grpmax-eligible	0.032%	3,125
African / African-American	0.00267%	37,502

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.Ser347Pro
Coding: c.1039T>C
MANE Select: NM_001382548
dbSNP: rs200378396
Type: single nucleotide variant
Location: chr5:146463697 (GRCh38)
Gene constraint: LOEUF 0.323 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.35 · 29 PDB
Residue 347: the 'disordered' region

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-ser347pro (accessed [today's date]).

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