Is IVD p.Ser116Phe (c.347C>T) pathogenic?

IVD p.Ser116Phe (c.347C>T) is classified Uncertain significance in IVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely pathogenic (0.9838); Absent from gnomAD v4.1.

How common is IVD p.Ser116Phe (c.347C>T) in the general population?

IVD p.Ser116Phe (c.347C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IVD p.Ser116Phe (c.347C>T)?

AlphaMissense predicts likely pathogenic (score 0.9838) — an in-silico prediction, not a clinical call.

IVD p.Ser116Phe

c.347C>T · VCV3339425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9838	likely pathogenic · top 8% in IVD
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -15.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S119F vs ClinVar S116F) — 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.Ser116Phe
Coding: c.347C>T
MANE Select: NM_002225
Type: single nucleotide variant
Location: chr15:40410688 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB
Residue 119 UniProt numbering: an α-helix

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

Similar variants

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
IVD c.456+2T>C Pathogenic ★★ same type
IVD c.457-2A>G 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-ser116phe (accessed [today's date]).

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