Is IFIH1 p.Pro103Ser (c.307C>T) pathogenic?

IFIH1 p.Pro103Ser (c.307C>T) is classified Uncertain significance in IFIH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.6281); Absent from gnomAD v4.1.

How common is IFIH1 p.Pro103Ser (c.307C>T) in the general population?

IFIH1 p.Pro103Ser (c.307C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFIH1 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely pathogenic (score 0.6281) — an in-silico prediction, not a clinical call.

IFIH1 p.Pro103Ser

c.307C>T · VCV3365956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6281	likely pathogenic
REVEL	0.374	indeterminate
SaProt	LLR -11.97	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 51 kb · p 0.00062 · regional, not allelic
Overall
CADD	24.9	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.

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: IFIH1
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_022168
Type: single nucleotide variant
Location: chr2:162318001 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 13 PDB

Full IFIH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFIH1 p.Pro103= Likely benign ★ same residue
IFIH1 p.Arg720Gln Pathogenic ★★ ⚠ same type
IFIH1 p.Arg779Cys Pathogenic ★★ ⚠ same type
IFIH1 p.Arg779His Pathogenic/Likely pathogenic ★★ ⚠ same type
IFIH1 p.Arg779Leu Pathogenic/Likely pathogenic ★★ same type
IFIH1 p.Arg822Gln Pathogenic/Likely pathogenic ★★ same type
IFIH1 p.Gly495Arg Likely pathogenic ★★ ⚠ same type
IFIH1 c.1525-1G>A Uncertain significance ★★ 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/ifih1-p-pro103ser (accessed [today's date]).

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