Is CNTN4 p.Pro236= (c.708G>T) pathogenic?

CNTN4 p.Pro236= (c.708G>T) is classified Likely benign in CNTN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.00167%, amr).

How common is CNTN4 p.Pro236= (c.708G>T) in the general population?

CNTN4 p.Pro236= (c.708G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

CNTN4 p.Pro236=

c.708G>T · rs577358521 · VCV740417

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -4.8
Overall
CADD	0.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 0.000186% 3/1,613,822 alleles · very rare exomes 3/1,461,534 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
South Asian	0.0011%	91,020
European (non-Finnish)	8.48e-05%	1,179,860

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: CNTN4
Protein: p.Pro236=
Coding: c.708G>T
MANE Select: NM_175607
dbSNP: rs577358521
Type: single nucleotide variant
Location: chr3:2883200 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.72
Residue 236: the ig-like c2-type 3 domain

Full CNTN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNTN4 p.Glu765Asp Uncertain significance ★★ ⚠ same type
CNTN4 c.1486+67C>A Benign ★★ same type
CNTN4 c.1487-86A>T Benign ★★ same type
CNTN4 c.1663-158A>G Benign ★★ same type
CNTN4 c.1663-174G>A Benign ★★ same type
CNTN4 c.1663-178C>T Benign ★★ same type
CNTN4 c.1663-212C>T Benign ★★ same type
CNTN4 c.1663-75C>G Benign ★★ 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/cntn4-p-pro236 (accessed [today's date]).

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