Is ASNS p.Cys207Phe (c.620G>T) pathogenic?

ASNS p.Cys207Phe (c.620G>T) is classified Uncertain significance in ASNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-26). AlphaMissense: likely benign (0.1364); Very rare (popmax 0.00339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Cys207Phe (c.620G>T)?

ASNS p.Cys207Phe (c.620G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.Cys207Phe (c.620G>T) in the general population?

ASNS p.Cys207Phe (c.620G>T) is very rare (popmax 0.00339%, nfe) (gnomAD).

What do computational predictors say about ASNS p.Cys207Phe (c.620G>T)?

AlphaMissense predicts likely benign (score 0.1364) — an in-silico prediction, not a clinical call.

ASNS p.Cys207Phe

c.620G>T · rs772174678 · VCV2415945

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1364	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -6.74	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 2.2	GERP -0.29, phastCons 0.97
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	15.7	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 0.00339% European (non-Finnish) · 40/1,180,014 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00248% 40/1,613,976 alleles · very rare

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: ASNS
Protein: p.Cys207Phe
Coding: c.620G>T
MANE Select: NM_001673
dbSNP: rs772174678
Type: single nucleotide variant
Location: chr7:97859266 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB

Full ASNS 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

ASNS c.1320+1G>C Likely pathogenic ★★ same condition
ASNS p.Arg465Ter Pathogenic/Likely pathogenic ★★ same condition
ASNS p.Arg550His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ASNS c.1238+3A>G Uncertain significance ★★ same condition
ASNS p.Ala303Glu Uncertain significance ★★ ⚠ same condition
ASNS p.Arg251Gly Uncertain significance ★★ ⚠ same condition
ASNS p.Arg392Lys Uncertain significance ★★ ⚠ same condition
ASNS p.Asn441Ser 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/asns-p-cys207phe (accessed [today's date]).

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