Is CSTA p.Ser7Phe (c.20C>T) pathogenic?

CSTA p.Ser7Phe (c.20C>T) is classified Uncertain significance in CSTA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: likely pathogenic (0.6281); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with CSTA p.Ser7Phe (c.20C>T)?

CSTA p.Ser7Phe (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSTA p.Ser7Phe (c.20C>T) in the general population?

CSTA p.Ser7Phe (c.20C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CSTA p.Ser7Phe (c.20C>T)?

AlphaMissense predicts likely pathogenic (score 0.6281) — an in-silico prediction, not a clinical call.

CSTA p.Ser7Phe

c.20C>T · rs751662705 · VCV3078433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6281	likely pathogenic
REVEL	0.035	moderately benign-leaning
SaProt	LLR -13.24	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -2
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.65 · regional, not allelic
Overall
CADD	18.41	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 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00178% 26/1,461,606 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
European (non-Finnish)	0.00195%	51,303

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: CSTA
Protein: p.Ser7Phe
Coding: c.20C>T
MANE Select: NM_005213
dbSNP: rs751662705
Type: single nucleotide variant
Location: chr3:122325312 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 93.57 · 14 PDB
Residue 7: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSTA p.Ala12Thr Uncertain significance ★ ⚠ same condition
CSTA p.Arg58Gln Uncertain significance ★ ⚠ same condition
CSTA p.Arg58Pro Uncertain significance ★ ⚠ same condition
CSTA p.Asp92Val Uncertain significance ★ ⚠ same condition
CSTA p.Gln17Arg Uncertain significance ★ ⚠ same condition
CSTA p.Gln42Arg Uncertain significance ★ ⚠ same condition
CSTA p.Glu94Lys Uncertain significance ★ ⚠ same condition
CSTA p.Lys30Asn Uncertain significance ★ ⚠ same condition

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/csta-p-ser7phe (accessed [today's date]).

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