Is C8G p.Phe194Val (c.580T>G) pathogenic?

C8G p.Phe194Val (c.580T>G) is classified Uncertain significance in C8G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.4907); Absent from gnomAD v4.1.

How common is C8G p.Phe194Val (c.580T>G) in the general population?

C8G p.Phe194Val (c.580T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C8G p.Phe194Val (c.580T>G)?

AlphaMissense predicts ambiguous (score 0.4907) — an in-silico prediction, not a clinical call.

C8G p.Phe194Val

c.580T>G · VCV4217471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4907	ambiguous
REVEL	0.066	moderately benign-leaning
SaProt	LLR -8.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,457 bp · p 0.046 · regional, not allelic
Overall
CADD	23.8	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: C8G
Protein: p.Phe194Val
Coding: c.580T>G
MANE Select: NM_000606
Type: single nucleotide variant
Location: chr9:136946674 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.06 · 15 PDB
Residue 194: an α-helix

Full C8G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8G p.Tyr181His Uncertain significance ★★ ⚠ same type
C8G c.276-3C>T Likely benign ★★ same type
C8G p.Arg69Gln Benign ★★ same type
C8G p.Val196Ile Likely benign ★★ same type
C8G p.Ala128Thr Uncertain significance ★ ⚠ same type
C8G p.Ala136Thr Uncertain significance ★ ⚠ same type
C8G p.Ala143Val Uncertain significance ★ ⚠ same type
C8G p.Ala16Val 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/c8g-p-phe194val (accessed [today's date]).

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