Is COL4A6 p.Phe330Val (c.988T>G) pathogenic?

COL4A6 p.Phe330Val (c.988T>G) is classified Uncertain significance in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.1023); Absent from gnomAD v4.1.

How common is COL4A6 p.Phe330Val (c.988T>G) in the general population?

COL4A6 p.Phe330Val (c.988T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A6 p.Phe330Val (c.988T>G)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

COL4A6 p.Phe330Val

c.988T>G · VCV3495536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -3.4, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 281 kb · p 0.15 · regional, not allelic
Overall
CADD	4.391	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 F331V vs ClinVar F330V) — 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: COL4A6
Protein: p.Phe330Val
Coding: c.988T>G
MANE Select: NM_033641
Type: single nucleotide variant
Location: chrX:108194548 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 330: the 'triple-helical region' region; the 'disordered' region

Full COL4A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL4A6 p.Phe330Leu Uncertain significance ★ ⚠ same residue
COL4A6 c.3970+5G>A Uncertain significance ★★ same type
COL4A6 p.Ala1275Thr Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala398Ser Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala421Gly Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala748Val Uncertain significance ★★ ⚠ same type
COL4A6 p.Ala886Thr Uncertain significance ★★ ⚠ same type
COL4A6 p.Arg1025Trp 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/col4a6-p-phe330val (accessed [today's date]).

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