Is COL4A6 p.Val952Phe (c.2854G>T) pathogenic?

COL4A6 p.Val952Phe (c.2854G>T) is classified Uncertain significance in COL4A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-19). AlphaMissense: likely benign (0.095); Absent from gnomAD v4.1.

How common is COL4A6 p.Val952Phe (c.2854G>T) in the general population?

COL4A6 p.Val952Phe (c.2854G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL4A6 p.Val952Phe (c.2854G>T)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

COL4A6 p.Val952Phe

c.2854G>T · rs2521864009 · VCV2157887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,195,628)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -7.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -0.3
Regional constraint	o/e 0.96	unconstrained · MANE · 281 kb · p 0.15 · regional, not allelic
Overall
CADD	6.887	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 V953F vs ClinVar V952F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,195,628). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL4A6
Protein: p.Val952Phe
Coding: c.2854G>T
MANE Select: NM_033641
dbSNP: rs2521864009
Type: single nucleotide variant
Location: chrX:108175192 (GRCh38)
Structure: AlphaFold pLDDT 48.27
Residue 952: 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.Val952= Likely benign ★★ 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-val952phe (accessed [today's date]).

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