Is SEC24C p.Arg950Trp (c.2848C>T) pathogenic?

SEC24C p.Arg950Trp (c.2848C>T) is classified Uncertain significance in SEC24C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.5114); Very rare (popmax 0.00203%, nfe).

How common is SEC24C p.Arg950Trp (c.2848C>T) in the general population?

SEC24C p.Arg950Trp (c.2848C>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about SEC24C p.Arg950Trp (c.2848C>T)?

AlphaMissense predicts ambiguous (score 0.5114) — an in-silico prediction, not a clinical call.

SEC24C p.Arg950Trp

c.2848C>T · VCV4581926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5114	ambiguous
REVEL	0.435	indeterminate
SaProt	LLR -17.14	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 10 kb · p 1.3e-13 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,016 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,614,004 alleles · very rare exomes 24/1,461,810 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,167
South Asian	0.0011%	91,054

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: SEC24C
Protein: p.Arg950Trp
Coding: c.2848C>T
MANE Select: NM_198597
Type: single nucleotide variant
Location: chr10:73770001 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.29 · 3 PDB
Residue 950: a β-strand

Full SEC24C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC24C c.1800-7T>C Benign ★★ same type
SEC24C c.3145-4G>A Benign ★★ same type
SEC24C c.850+10T>G Benign ★★ same type
SEC24C p.Ala566= Benign ★★ same type
SEC24C p.Gly257= Benign/Likely benign ★★ same type
SEC24C p.Pro255Ala Benign ★★ same type
SEC24C p.Pro958= Likely benign ★★ same type
SEC24C p.Thr870= Likely benign ★★ 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/sec24c-p-arg950trp (accessed [today's date]).

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