Is IVD p.Ser155Arg (c.465T>G) pathogenic?

IVD p.Ser155Arg (c.465T>G) is classified Uncertain significance in IVD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: ambiguous (0.4042); Absent from gnomAD v4.1.

How common is IVD p.Ser155Arg (c.465T>G) in the general population?

IVD p.Ser155Arg (c.465T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IVD p.Ser155Arg (c.465T>G)?

AlphaMissense predicts ambiguous (score 0.4042) — an in-silico prediction, not a clinical call.

IVD p.Ser155Arg

c.465T>G · VCV4687263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4042 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4042	ambiguous
REVEL	0.485	indeterminate
SaProt	LLR -11.32	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.7	GERP -3.5
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S158R vs ClinVar S155R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IVD
Protein: p.Ser155Arg
Coding: c.465T>G
MANE Select: NM_002225
Type: single nucleotide variant
Location: chr15:40411268 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB
Residue 158 UniProt numbering: an α-helix

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

Similar variants

IVD p.Ser155Asn Uncertain significance ★★ ⚠ same residue
IVD p.Ser155Gly Uncertain significance ★ ⚠ same residue
IVD c.144+1G>A Likely pathogenic ★★ same type
IVD c.144+1G>C Pathogenic ★★ same type
IVD c.286+2T>C Pathogenic/Likely pathogenic ★★ same type
IVD c.286+5G>T Likely pathogenic ★★ same type
IVD c.287-1G>A Pathogenic/Likely pathogenic ★★ same type
IVD c.287-2A>G Pathogenic/Likely 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/ivd-p-ser155arg (accessed [today's date]).

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