Is CDCA7L p.Phe293Ser (c.878T>C) pathogenic?

CDCA7L p.Phe293Ser (c.878T>C) is classified Uncertain significance in CDCA7L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3752); Very rare (popmax 0.00268%, afr).

How common is CDCA7L p.Phe293Ser (c.878T>C) in the general population?

CDCA7L p.Phe293Ser (c.878T>C) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about CDCA7L p.Phe293Ser (c.878T>C)?

AlphaMissense predicts ambiguous (score 0.3752) — an in-silico prediction, not a clinical call.

CDCA7L p.Phe293Ser

c.878T>C · VCV4223544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3752	ambiguous
REVEL	0.077	moderately benign-leaning
SaProt	LLR -2.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.2	GERP 0.95, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 43 kb · p 0.0085 · regional, not allelic
Overall
CADD	22.8	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 0.00268% African / African-American · 2/74,546 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000124% 2/1,610,018 alleles · very rare exomes 0/1,457,852 · genomes 2/152,166 · joint denominator

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.Phe293Ser
Coding: c.878T>C
MANE Select: NM_018719
Type: single nucleotide variant
Location: chr7:21906332 (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-phe293ser (accessed [today's date]).

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