Is C6 p.Ile314Ser (c.941T>G) pathogenic?

C6 p.Ile314Ser (c.941T>G) is classified Uncertain significance in C6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: ambiguous (0.5576); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with C6 p.Ile314Ser (c.941T>G)?

C6 p.Ile314Ser (c.941T>G) is associated with Inborn genetic diseases (ClinVar).

How common is C6 p.Ile314Ser (c.941T>G) in the general population?

C6 p.Ile314Ser (c.941T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C6 p.Ile314Ser (c.941T>G)?

AlphaMissense predicts ambiguous (score 0.5576) — an in-silico prediction, not a clinical call.

C6 p.Ile314Ser

c.941T>G · VCV3826396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5576 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5576	ambiguous
REVEL	0.654	pathogenic-leaning
SaProt	LLR -3.48	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 60 kb · p 0.0034 · regional, not allelic
Overall
CADD	23.9	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

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: C6
Protein: p.Ile314Ser
Coding: c.941T>G
MANE Select: NM_000065
Type: single nucleotide variant
Location: chr5:41176702 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 314: a β-strand; the macpf domain

Full C6 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

C6 p.Ala396Gly Uncertain significance ★★ ⚠ same condition
C6 p.Ala456Thr Uncertain significance ★★ ⚠ same condition
C6 p.Ala500Ser Uncertain significance ★★ ⚠ same condition
C6 p.Arg108His Uncertain significance ★★ ⚠ same condition
C6 p.Arg145His Uncertain significance ★★ ⚠ same condition
C6 p.Arg150His Uncertain significance ★★ ⚠ same condition
C6 p.Arg182Gln Uncertain significance ★★ ⚠ same condition
C6 p.Arg356Gln 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/c6-p-ile314ser (accessed [today's date]).

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