Is BCAS4 p.Ala6Val (c.17C>T) pathogenic?

BCAS4 p.Ala6Val (c.17C>T) is classified Uncertain significance in BCAS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1584); Very rare (popmax 0.00852%, nfe).

How common is BCAS4 p.Ala6Val (c.17C>T) in the general population?

BCAS4 p.Ala6Val (c.17C>T) is very rare (popmax 0.00852%, nfe) (gnomAD).

What do computational predictors say about BCAS4 p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.1584) — an in-silico prediction, not a clinical call.

BCAS4 p.Ala6Val

c.17C>T · VCV4645416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00852%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1584	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.77	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 1.1	GERP -3, phastCons 0.6
Regional constraint	o/e 0.94	unconstrained · MANE · 82 kb · p 0.36 · regional, not allelic
Overall
CADD	17.05	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 A36V vs ClinVar A6V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00852% European (non-Finnish) · 96/1,126,410 alleles

Filtering AF 0.00713% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00663%

Overall 0.00666% 100/1,502,380 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00852%	11,733
Admixed American	0.00208%	48,118
Remaining individualsnot grpmax-eligible	0.00172%	58,000
African / African-American	0.00143%	69,700
South Asian	0.00125%	80,092

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: BCAS4
Protein: p.Ala6Val
Coding: c.17C>T
MANE Select: NM_198799
Type: single nucleotide variant
Location: chr20:50795100 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40
Residue 6: the 'disordered' region

Full BCAS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS4 p.Ser130Thr Benign ★★ same type
BCAS4 p.Ser130Tyr Benign/Likely benign ★★ same type
BCAS4 p.Thr142Met Likely benign ★★ same type
BCAS4 c.-15C>T Uncertain significance ★ ⚠ same type
BCAS4 c.-6C>T Uncertain significance ★ ⚠ same type
BCAS4 p.Ala118Ser Uncertain significance ★ ⚠ same type
BCAS4 p.Ala126Thr Uncertain significance ★ ⚠ same type
BCAS4 p.Ala29Ser 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/bcas4-p-ala6val (accessed [today's date]).

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