Is SEC24D p.Pro143= (c.429C>T) pathogenic?

SEC24D p.Pro143= (c.429C>T) is classified Benign/Likely benign in SEC24D (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.258%, sas).

How common is SEC24D p.Pro143= (c.429C>T) in the general population?

SEC24D p.Pro143= (c.429C>T) is rare (popmax 0.258%, sas) (gnomAD).

SEC24D p.Pro143=

c.429C>T · rs150602522 · VCV721074

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, sas)

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 -0.048	GERP -0.92, phastCons 0.33
Overall
CADD	7.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% South Asian · 235/91,080 alleles

Filtering AF 0.231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.206% 3,332/1,614,070 alleles · rare exomes 3,099/1,461,762 · genomes 233/152,308 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.354%	283
South Asiangrpmax	0.258%	388
European (non-Finnish)	0.228%	438
Remaining individualsnot grpmax-eligible	0.144%	695
Middle Eastern	0.132%	758
Admixed American	0.0933%	1,072
African / African-American	0.0293%	3,411
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SEC24D
Protein: p.Pro143=
Coding: c.429C>T
MANE Select: NM_014822
dbSNP: rs150602522
Type: single nucleotide variant
Location: chr4:118815695 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 6 PDB
Residue 143: the 'disordered' region

Full SEC24D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC24D c.1181-1G>C Likely pathogenic ★★ same type
SEC24D c.1824+1G>T Likely pathogenic ★★ same type
SEC24D p.Arg993Ter Pathogenic/Likely pathogenic ★★ same type
SEC24D p.Ser1015Phe Pathogenic ★★ same type
SEC24D p.Ala218Val Uncertain significance ★★ ⚠ same type
SEC24D p.Ala570Val Uncertain significance ★★ ⚠ same type
SEC24D p.Ala774Asp Uncertain significance ★★ ⚠ same type
SEC24D p.Ala94Thr 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/sec24d-p-pro143 (accessed [today's date]).

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