Is CDCA7L p.Val256Ala (c.767T>C) pathogenic?

CDCA7L p.Val256Ala (c.767T>C) is classified Uncertain significance in CDCA7L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0684); Ultra-rare (popmax 0.0671%, sas).

How common is CDCA7L p.Val256Ala (c.767T>C) in the general population?

CDCA7L p.Val256Ala (c.767T>C) is ultra-rare (popmax 0.0671%, sas) (gnomAD).

What do computational predictors say about CDCA7L p.Val256Ala (c.767T>C)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

CDCA7L p.Val256Ala

c.767T>C · VCV4650953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0671%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -4.3
Regional constraint	o/e 1.11	unconstrained · MANE · 43 kb · p 0.0085 · regional, not allelic
Overall
CADD	7.787	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

Grpmax group 0.0671% South Asian · 61/90,868 alleles

Filtering AF 0.0536% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0487%

Overall 0.0041% 66/1,610,142 alleles · ultra-rare exomes 60/1,458,006 · genomes 6/152,136 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0671%	1,490
Remaining individualsnot grpmax-eligible	0.00803%	12,453

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.Val256Ala
Coding: c.767T>C
MANE Select: NM_018719
Type: single nucleotide variant
Location: chr7:21906443 (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.Arg4449Cys Uncertain significance ★★ ⚠ same type
DNAH11 p.Gln4474Glu Uncertain significance ★★ ⚠ same type
DNAH11 p.Gln4474Lys Uncertain significance ★★ ⚠ same type
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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-val256ala (accessed [today's date]).

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