Is CDC7 p.Ser71Thr (c.211T>A) pathogenic?

CDC7 p.Ser71Thr (c.211T>A) is classified Uncertain significance in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.2242); Ultra-rare (popmax 0.0344%, amr).

How common is CDC7 p.Ser71Thr (c.211T>A) in the general population?

CDC7 p.Ser71Thr (c.211T>A) is ultra-rare (popmax 0.0344%, amr) (gnomAD).

What do computational predictors say about CDC7 p.Ser71Thr (c.211T>A)?

AlphaMissense predicts likely benign (score 0.2242) — an in-silico prediction, not a clinical call.

CDC7 p.Ser71Thr

c.211T>A · rs778701504 · VCV2397138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2242 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2242	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.58, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	22.4	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 0.0344% Admixed American · 19/55,214 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00125% 20/1,597,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0344%	2,906
Remaining individualsnot grpmax-eligible	0.00162%	61,762

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: CDC7
Protein: p.Ser71Thr
Coding: c.211T>A
MANE Select: NM_003503
dbSNP: rs778701504
Type: single nucleotide variant
Location: chr1:91508273 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 71: the protein kinase domain; a β-strand; a binding site

Full CDC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC7 p.Ser71Cys Uncertain significance ★ ⚠ same residue
CDC7 c.-124A>G Benign ★★ same type
CDC7 p.Ala254Gly Uncertain significance ★ ⚠ same type
CDC7 p.Ala254Ser Uncertain significance ★ ⚠ same type
CDC7 p.Ala355Val Uncertain significance ★ ⚠ same type
CDC7 p.Ala38Glu Uncertain significance ★ ⚠ same type
CDC7 p.Ala38Thr Uncertain significance ★ ⚠ same type
CDC7 p.Ala50Val 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/cdc7-p-ser71thr (accessed [today's date]).

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