Is TRAPPC6B p.Phe72Ser (c.215T>C) pathogenic?

TRAPPC6B p.Phe72Ser (c.215T>C) is classified Uncertain significance in TRAPPC6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely pathogenic (0.9946); Very rare (popmax 0.00269%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC6B p.Phe72Ser (c.215T>C)?

TRAPPC6B p.Phe72Ser (c.215T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC6B p.Phe72Ser (c.215T>C) in the general population?

TRAPPC6B p.Phe72Ser (c.215T>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about TRAPPC6B p.Phe72Ser (c.215T>C)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

TRAPPC6B p.Phe72Ser

c.215T>C · VCV3973051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -16.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 20 kb · p 0.12 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00269% African / African-American · 2/74,400 alleles

Filtering AF 0.000804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000651%

Overall 0.00118% 19/1,604,092 alleles · very rare exomes 16/1,451,912 · genomes 3/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,200
Remaining individualsnot grpmax-eligible	0.00161%	62,122
European (non-Finnish)	0.00136%	73,623

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: TRAPPC6B
Protein: p.Phe72Ser
Coding: c.215T>C
MANE Select: NM_001079537
Type: single nucleotide variant
Location: chr14:39158337 (GRCh38)
Gene constraint: LOEUF 1.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.93 · 3 PDB
Residue 72: a UniProt-annotated variant site (in nedmeba); an α-helix

Full TRAPPC6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAPPC6B p.Arg31Ter Pathogenic/Likely pathogenic ★★ same condition
TRAPPC6B p.Asp54Val Uncertain significance ★★ ⚠ same condition
TRAPPC6B p.Lys98Arg Uncertain significance ★★ ⚠ same condition
TRAPPC6B p.Thr75Ala Likely benign ★★ same condition
TRAPPC6B p.Arg100Leu Uncertain significance ★ ⚠ same condition
TRAPPC6B p.Arg42Gln Uncertain significance ★ ⚠ same condition
TRAPPC6B p.Asn83His Uncertain significance ★ ⚠ same condition
TRAPPC6B p.Asp3Glu Uncertain significance ★ ⚠ same condition

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/trappc6b-p-phe72ser (accessed [today's date]).

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