Is DCTN4 p.Pro236Ser (c.706C>T) pathogenic?

DCTN4 p.Pro236Ser (c.706C>T) is classified Uncertain significance in DCTN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1179); Very rare (popmax 0.00671%, afr).

How common is DCTN4 p.Pro236Ser (c.706C>T) in the general population?

DCTN4 p.Pro236Ser (c.706C>T) is very rare (popmax 0.00671%, afr) (gnomAD).

What do computational predictors say about DCTN4 p.Pro236Ser (c.706C>T)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

DCTN4 p.Pro236Ser

c.706C>T · rs369098676 · VCV3080656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.0058 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.00671% African / African-American · 5/74,470 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000501% 8/1,596,852 alleles · very rare exomes 5/1,444,792 · genomes 3/152,060 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00671%	14,894
Admixed American	0.00167%	59,710
South Asian	0.00111%	90,304
European (non-Finnish)	8.58e-05%	1,165,250

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: DCTN4
Protein: p.Pro236Ser
Coding: c.706C>T
MANE Select: NM_016221
dbSNP: rs369098676
Type: single nucleotide variant
Location: chr5:150731062 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 2 PDB

Full DCTN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCTN4 p.Pro236Leu Uncertain significance ★ ⚠ same residue
DCTN4 p.Ala195Thr Uncertain significance ★ ⚠ same type
DCTN4 p.Ala221Thr Uncertain significance ★ ⚠ same type
DCTN4 p.Ala22Val Uncertain significance ★ ⚠ same type
DCTN4 p.Ala2Ser Uncertain significance ★ ⚠ same type
DCTN4 p.Arg143Trp Uncertain significance ★ ⚠ same type
DCTN4 p.Arg162Gln Uncertain significance ★ ⚠ same type
DCTN4 p.Arg169Gln 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/dctn4-p-pro236ser (accessed [today's date]).

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