Is VCAN p.Ser970Phe (c.2909C>T) pathogenic?

VCAN p.Ser970Phe (c.2909C>T) is classified Conflicting classifications of pathogenicity in VCAN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1648); Rare (popmax 0.189%, afr); Associated with Inborn genetic diseases.

What condition is associated with VCAN p.Ser970Phe (c.2909C>T)?

VCAN p.Ser970Phe (c.2909C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VCAN p.Ser970Phe (c.2909C>T) in the general population?

VCAN p.Ser970Phe (c.2909C>T) is rare (popmax 0.189%, afr) (gnomAD).

What do computational predictors say about VCAN p.Ser970Phe (c.2909C>T)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

VCAN p.Ser970Phe

c.2909C>T · rs150708651 · VCV1078922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.189%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 0.073
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% African / African-American · 142/75,044 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.00917% 148/1,613,936 alleles · rare exomes 69/1,461,614 · genomes 79/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.189%	528
Remaining individualsnot grpmax-eligible	0.0096%	10,415

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: VCAN
Protein: p.Ser970Phe
Coding: c.2909C>T
MANE Select: NM_004385
dbSNP: rs150708651
Type: single nucleotide variant
Location: chr5:83521215 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 970: the 'gag-alpha (glucosaminoglycan attachment domain)' region

Full VCAN 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

VCAN p.Ala1048Val Uncertain significance ★★ ⚠ same condition
VCAN p.Ala1228Thr Uncertain significance ★★ ⚠ same condition
VCAN p.Ala1314Gly Uncertain significance ★★ same condition
VCAN p.Ala1533Gly Uncertain significance ★★ ⚠ same condition
VCAN p.Ala2446Val Uncertain significance ★★ ⚠ same condition
VCAN p.Ala275Ser Uncertain significance ★★ ⚠ same condition
VCAN p.Ala2772Thr Uncertain significance ★★ ⚠ same condition
VCAN p.Ala2783Thr 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/vcan-p-ser970phe (accessed [today's date]).

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