Is CNTNAP1 p.Val385Ala (c.1154T>C) pathogenic?

CNTNAP1 p.Val385Ala (c.1154T>C) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely pathogenic (0.6645); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CNTNAP1 p.Val385Ala (c.1154T>C)?

CNTNAP1 p.Val385Ala (c.1154T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CNTNAP1 p.Val385Ala (c.1154T>C) in the general population?

CNTNAP1 p.Val385Ala (c.1154T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CNTNAP1 p.Val385Ala (c.1154T>C)?

AlphaMissense predicts likely pathogenic (score 0.6645) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Val385Ala

c.1154T>C · rs2543792796 · VCV3146818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6645	likely pathogenic
REVEL	0.638	indeterminate
SaProt	LLR -10.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 0.000205% 3/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,086

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: CNTNAP1
Protein: p.Val385Ala
Coding: c.1154T>C
MANE Select: NM_003632
dbSNP: rs2543792796
Type: single nucleotide variant
Location: chr17:42687829 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51

Full CNTNAP1 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

CNTNAP1 p.Ala1322Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala254Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala40Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala887Val Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1022Ser Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1073His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1150Cys Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1153Gln 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/cntnap1-p-val385ala (accessed [today's date]).

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