Is SEC24D p.Pro473Ser (c.1417C>T) pathogenic?

SEC24D p.Pro473Ser (c.1417C>T) is classified Uncertain significance in SEC24D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-27). AlphaMissense: likely benign (0.3182); Very rare (popmax 0.00586%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SEC24D p.Pro473Ser (c.1417C>T)?

SEC24D p.Pro473Ser (c.1417C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SEC24D p.Pro473Ser (c.1417C>T) in the general population?

SEC24D p.Pro473Ser (c.1417C>T) is very rare (popmax 0.00586%, nfe) (gnomAD).

What do computational predictors say about SEC24D p.Pro473Ser (c.1417C>T)?

AlphaMissense predicts likely benign (score 0.3182) — an in-silico prediction, not a clinical call.

SEC24D p.Pro473Ser

c.1417C>T · VCV3439184

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00586%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3182	likely benign
REVEL	0.633	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 110 kb · p 0.00018 · regional, not allelic
Overall
CADD	27.9	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 0.00586% European (non-Finnish) · 69/1,177,120 alleles

Filtering AF 0.00471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00432%

Overall 0.00436% 70/1,604,554 alleles · very rare exomes 61/1,452,476 · genomes 9/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00586%	17,060
African / African-American	0.00135%	74,266

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.Pro473Ser
Coding: c.1417C>T
MANE Select: NM_014822
Type: single nucleotide variant
Location: chr4:118757725 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC24D c.1824+1G>T Likely pathogenic ★★ same condition
SEC24D p.Ala218Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala570Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala774Asp Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala94Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Arg365Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp1018Asn Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp429Tyr 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/sec24d-p-pro473ser (accessed [today's date]).

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