Is CDCA7L p.Pro382Leu (c.1145C>T) pathogenic?

CDCA7L p.Pro382Leu (c.1145C>T) is classified Uncertain significance in CDCA7L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.9567); Very rare (popmax 0.00267%, afr).

How common is CDCA7L p.Pro382Leu (c.1145C>T) in the general population?

CDCA7L p.Pro382Leu (c.1145C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CDCA7L p.Pro382Leu (c.1145C>T)?

AlphaMissense predicts likely pathogenic (score 0.9567) — an in-silico prediction, not a clinical call.

CDCA7L p.Pro382Leu

c.1145C>T · VCV3998721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9567 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9567	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 43 kb · p 0.0085 · regional, not allelic
Overall
CADD	31.0	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 0.00267% African / African-American · 2/74,864 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00211% 34/1,612,946 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,432
European (non-Finnish)	0.00263%	38,050
Remaining individualsnot grpmax-eligible	0.0016%	62,434

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: CDCA7L
Protein: p.Pro382Leu
Coding: c.1145C>T
MANE Select: NM_018719
Type: single nucleotide variant
Location: chr7:21904162 (GRCh38)
Gene constraint: LOEUF 0.983 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.23 · 2 PDB

Full CDCA7L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH11 p.Pro4458Leu Pathogenic/Likely pathogenic ★★ same type
DNAH11 p.Arg4437Cys Uncertain significance ★★ ⚠ same type
DNAH11 p.Arg4437His Uncertain significance ★★ ⚠ same type
DNAH11 p.Arg4449Cys Uncertain significance ★★ ⚠ same type
DNAH11 p.Gln4474Glu Uncertain significance ★★ ⚠ same type
DNAH11 p.Gln4474Lys Uncertain significance ★★ ⚠ same type
DNAH11 p.Glu4477Lys Uncertain significance ★★ ⚠ same type
DNAH11 p.Glu4500Gly 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/cdca7l-p-pro382leu (accessed [today's date]).

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