Is TRAPPC12 p.Ser414= (c.1242C>T) pathogenic?

TRAPPC12 p.Ser414= (c.1242C>T) is classified Benign in TRAPPC12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Common (popmax 32.3%, eas) — too common for a highly-penetrant pathogenic allele.

TRAPPC12 p.Ser414=

Q: How common is TRAPPC12 p.Ser414= (c.1242C>T) in the general population?

TRAPPC12 p.Ser414= (c.1242C>T) is common (popmax 32.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1242C>T · rs1132171 · VCV1600346

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 32.3%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.225	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.6
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.3% East Asian · 14,466/44,780 alleles

Filtering AF 31.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.7%

Overall 2.81% 45,262/1,613,194 alleles · common exomes 40,997/1,460,856 · genomes 4,265/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	32.3%	3
South Asian	16.5%	6
Finnishnot grpmax-eligible	6.43%	16
Remaining individualsnot grpmax-eligible	4.04%	25
Admixed American	3.79%	26
Middle Eastern	1.2%	83
Ashkenazi Jewishnot grpmax-eligible	0.686%	146
European (non-Finnish)	0.534%	187
African / African-American	0.413%	242

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: TRAPPC12
Protein: p.Ser414=
Coding: c.1242C>T
MANE Select: NM_016030
dbSNP: rs1132171
Type: single nucleotide variant
Location: chr2:3421958 (GRCh38)
Gene constraint: LOEUF 1.192 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52

Full TRAPPC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAPPC12 p.Ala627Val Pathogenic/Likely pathogenic ★★ same type
TRAPPC12 c.1531-3C>T Uncertain significance ★★ same type
TRAPPC12 c.1603+5G>C Uncertain significance ★★ same type
TRAPPC12 p.Ala309Val Uncertain significance ★★ ⚠ same type
TRAPPC12 p.Ala485Thr Uncertain significance ★★ ⚠ same type
TRAPPC12 p.Ala637Val Uncertain significance ★★ ⚠ same type
TRAPPC12 p.Arg166Ser Uncertain significance ★★ ⚠ same type
TRAPPC12 p.Arg533Gly 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/trappc12-p-ser414 (accessed [today's date]).

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