Is SEC23A p.Pro364= (c.1092C>T) pathogenic?

SEC23A p.Pro364= (c.1092C>T) is classified Benign in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Low-frequency (popmax 2.09%, afr); Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Pro364= (c.1092C>T)?

SEC23A p.Pro364= (c.1092C>T) is associated with craniolenticulosutural dysplasia (ClinVar).

How common is SEC23A p.Pro364= (c.1092C>T) in the general population?

SEC23A p.Pro364= (c.1092C>T) is low-frequency (popmax 2.09%, afr) (gnomAD).

SEC23A p.Pro364=

c.1092C>T · rs77375580 · VCV771900

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

Conditions

craniolenticulosutural dysplasia

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 2.1	GERP -3.8, phastCons 1
Overall
CADD	7.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,562/74,784 alleles

Filtering AF 2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.97%

Overall 0.129% 2,063/1,602,822 alleles · low-frequency exomes 1,135/1,450,548 · genomes 928/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Ashkenazi Jewishnot grpmax-eligible	0.603%	166
Remaining individualsnot grpmax-eligible	0.188%	531
Admixed American	0.127%	790
Middle Eastern	0.0828%	1,208
European (non-Finnish)	0.0104%	9,591
South Asian	0.0033%	30,274

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: SEC23A
Protein: p.Pro364=
Coding: c.1092C>T
MANE Select: NM_006364
dbSNP: rs77375580
Type: single nucleotide variant
Location: chr14:39074426 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB
Residue 364: an α-helix

Full SEC23A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

craniolenticulosutural dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC23A p.Ala284Pro Uncertain significance ★★ ⚠ same condition
SEC23A p.Ala478Ser Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg123Cys Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg476His Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg67His Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg716Cys Uncertain significance ★★ ⚠ same condition
SEC23A p.Asn680Asp Uncertain significance ★★ ⚠ same condition
SEC23A p.Cys180Tyr 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/sec23a-p-pro364 (accessed [today's date]).

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