Is SERPING1 p.Asp304Val (c.911A>T) pathogenic?

SERPING1 p.Asp304Val (c.911A>T) is classified Uncertain significance in SERPING1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-09). AlphaMissense: likely benign (0.2052); Very rare (popmax 8.47e-05%, nfe).

How common is SERPING1 p.Asp304Val (c.911A>T) in the general population?

SERPING1 p.Asp304Val (c.911A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SERPING1 p.Asp304Val (c.911A>T)?

AlphaMissense predicts likely benign (score 0.2052) — an in-silico prediction, not a clinical call.

SERPING1 p.Asp304Val

c.911A>T · rs2495442163 · VCV2015554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2052	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.087, phastCons 0.89
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	17.28	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 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.2e-05% 1/1,614,158 alleles · very rare exomes 1/1,461,888 · genomes 0/152,270 · 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: SERPING1
Protein: p.Asp304Val
Coding: c.911A>T
MANE Select: NM_000062
dbSNP: rs2495442163
Type: single nucleotide variant
Location: chr11:57606429 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 5 PDB
Residue 304: an α-helix

Full SERPING1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SERPING1 p.Asp304Gly Likely pathogenic ★ same residue
SERPING1 p.Asp304His Uncertain significance ★ ⚠ same residue
SERPING1 p.Asp304_Thr308delinsAla Uncertain significance ★ same residue
SERPING1 c.1030-1G>T Pathogenic ★★ same type
SERPING1 c.51+1G>T Pathogenic ★★ same type
SERPING1 c.51+3A>C Pathogenic/Likely pathogenic ★★ same type
SERPING1 c.51+3A>G Pathogenic ★★ same type
SERPING1 c.52-1G>A Pathogenic ★★ 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/serping1-p-asp304val (accessed [today's date]).

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