Is ACAN p.Ala1271Val (c.3812C>T) pathogenic?

ACAN p.Ala1271Val (c.3812C>T) is classified Uncertain significance in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-06). AlphaMissense: likely pathogenic (0.6367); Absent from gnomAD v4.1.

How common is ACAN p.Ala1271Val (c.3812C>T) in the general population?

ACAN p.Ala1271Val (c.3812C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAN p.Ala1271Val (c.3812C>T)?

AlphaMissense predicts likely pathogenic (score 0.6367) — an in-silico prediction, not a clinical call.

ACAN p.Ala1271Val

c.3812C>T · rs1402483015 · VCV497283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6367 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6367	likely pathogenic
REVEL	0.142	moderately benign-leaning
SaProt	LLR -10.65	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP -1.1, phastCons 0.009
Regional constraint	o/e 0.38	unconstrained · MANE · 1,434 bp · p 4e-11 · regional, not allelic
Overall
CADD	14.1	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: ACAN
Protein: p.Ala1271Val
Coding: c.3812C>T
MANE Select: NM_001369268
dbSNP: rs1402483015
Type: single nucleotide variant
Location: chr15:88856397 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 1271: the 'cs-1' region; the '35 x 19 aa approximate tandem repeats of e-[ivdg]-[lv]-[ev]-[gti]-[sta]-[atv]-[sp]-[ga]-[vifad]-[gedl]-[de]-[lvi]-[sg]-[gerk]-[lv]-p-s-g' region

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

Similar variants

ACAN c.1733-2A>G Likely pathogenic ★★ same type
ACAN c.630-13G>A Pathogenic ★★ same type
ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
ACAN p.Arg236Ter Pathogenic ★★ same type
ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
ACAN p.Arg394Ter Pathogenic ★★ same type
ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same type
ACAN p.Asp2419Asn Likely pathogenic ★★ 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/acan-p-ala1271val (accessed [today's date]).

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