Is CDCA7L p.Ile409Val (c.1225A>G) pathogenic?

CDCA7L p.Ile409Val (c.1225A>G) is classified Uncertain significance in CDCA7L (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.1104); Absent from gnomAD v4.1.

How common is CDCA7L p.Ile409Val (c.1225A>G) in the general population?

CDCA7L p.Ile409Val (c.1225A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDCA7L p.Ile409Val (c.1225A>G)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CDCA7L p.Ile409Val

c.1225A>G · rs2534187562 · VCV2229418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 43 kb · p 0.0085 · regional, not allelic
Overall
CADD	20.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDCA7L
Protein: p.Ile409Val
Coding: c.1225A>G
MANE Select: NM_018719
dbSNP: rs2534187562
Type: single nucleotide variant
Location: chr7:21903087 (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

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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-ile409val (accessed [today's date]).

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