Is COL4A3 p.Phe962= (c.2886C>T) pathogenic?

COL4A3 p.Phe962= (c.2886C>T) is classified Benign/Likely benign in COL4A3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-28). Rare (popmax 0.376%, afr); Associated with Alport syndrome.

What condition is associated with COL4A3 p.Phe962= (c.2886C>T)?

COL4A3 p.Phe962= (c.2886C>T) is associated with Alport syndrome (ClinVar).

How common is COL4A3 p.Phe962= (c.2886C>T) in the general population?

COL4A3 p.Phe962= (c.2886C>T) is rare (popmax 0.376%, afr) (gnomAD).

How is Alport syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL4A3 p.Phe962=

c.2886C>T · rs77846212 · VCV595859

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.376%, afr)

Conditions

Alport syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.52	GERP -4.6
Overall
CADD	6.735	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.376% African / African-American · 282/74,930 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.326%

Overall 0.0425% 685/1,612,472 alleles · rare exomes 504/1,460,380 · genomes 181/152,092 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.376%	266
Admixed American	0.276%	363
Middle Eastern	0.116%	865
Remaining individualsnot grpmax-eligible	0.0848%	1,179
European (non-Finnish)	0.0149%	6,700
South Asian	0.0022%	45,383

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL4A3
Protein: p.Phe962=
Coding: c.2886C>T
MANE Select: NM_000091
dbSNP: rs77846212
Type: single nucleotide variant
Location: chr2:227289154 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 48.64 · 2 PDB
Residue 962: the 'triple-helical region' region; the 'disordered' region

Full COL4A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Alport syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alport syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

COL4A3 c.1114+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1408+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1504+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL4A3 c.1927+1G>A Likely pathogenic ★★ same condition
COL4A3 c.2020+1G>T Likely pathogenic ★★ same condition
COL4A3 c.2224-2A>G Likely pathogenic ★★ same condition
COL4A3 c.2375-2A>G Likely pathogenic ★★ 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/col4a3-p-phe962 (accessed [today's date]).

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