Is SEC23A p.Val173= (c.519T>G) pathogenic?

SEC23A p.Val173= (c.519T>G) is classified Likely benign in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). Ultra-rare (popmax 0.0746%, sas); Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Val173= (c.519T>G)?

SEC23A p.Val173= (c.519T>G) is associated with craniolenticulosutural dysplasia (ClinVar).

How common is SEC23A p.Val173= (c.519T>G) in the general population?

SEC23A p.Val173= (c.519T>G) is ultra-rare (popmax 0.0746%, sas) (gnomAD).

SEC23A p.Val173=

c.519T>G · rs750776856 · VCV2811557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0746%, sas)

Conditions

craniolenticulosutural dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -3.5
Overall
CADD	6.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0746% South Asian · 68/91,092 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0551%

Overall 0.00421% 68/1,613,950 alleles · ultra-rare exomes 67/1,461,742 · genomes 1/152,208 · joint denominator

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.Val173=
Coding: c.519T>G
MANE Select: NM_006364
dbSNP: rs750776856
Type: single nucleotide variant
Location: chr14:39091561 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB
Residue 173: a β-strand

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-val173 (accessed [today's date]).

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