Is SEC23IP p.Pro114= (c.342C>T) pathogenic?

SEC23IP p.Pro114= (c.342C>T) is classified Likely benign in SEC23IP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-26). Ultra-rare (popmax 0.032%, afr); Associated with SEC23IP-related disorder.

What condition is associated with SEC23IP p.Pro114= (c.342C>T)?

SEC23IP p.Pro114= (c.342C>T) is associated with SEC23IP-related disorder (ClinVar).

How common is SEC23IP p.Pro114= (c.342C>T) in the general population?

SEC23IP p.Pro114= (c.342C>T) is ultra-rare (popmax 0.032%, afr) (gnomAD).

SEC23IP p.Pro114=

c.342C>T · rs187525199 · VCV3036226

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Conditions

SEC23IP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.035	GERP -2.3, phastCons 0.89
Overall
CADD	5.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/75,062 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00167% 27/1,614,192 alleles · ultra-rare exomes 22/1,461,868 · genomes 5/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,128
Admixed American	0.00167%	60,018
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,090

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: SEC23IP
Protein: p.Pro114=
Coding: c.342C>T
MANE Select: NM_007190
dbSNP: rs187525199
Type: single nucleotide variant
Location: chr10:119898605 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.95
Residue 114: the 'interaction with sec23a' region

Full SEC23IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SEC23IP-related disorder

Similar variants

SEC23IP p.Pro114Leu Uncertain significance ★ ⚠ same residue
SEC23IP p.Gln270Ter Uncertain significance same condition
SEC23IP p.Tyr300Ter Uncertain significance same condition
SEC23IP c.1102-7A>C Likely benign same condition
SEC23IP c.1312+3G>A Likely benign same condition
SEC23IP c.1403-9C>A Benign same condition
SEC23IP c.2313+10C>T Benign same condition
SEC23IP c.2922-4A>T Benign 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/sec23ip-p-pro114 (accessed [today's date]).

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