Is ASNS p.Phe174Val (c.520T>G) pathogenic?

ASNS p.Phe174Val (c.520T>G) is classified Uncertain significance in ASNS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-17). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0176%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASNS p.Phe174Val (c.520T>G)?

ASNS p.Phe174Val (c.520T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ASNS p.Phe174Val (c.520T>G) in the general population?

ASNS p.Phe174Val (c.520T>G) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about ASNS p.Phe174Val (c.520T>G)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

ASNS p.Phe174Val

c.520T>G · rs560439034 · VCV2121311

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.45	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 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 5.1e-10 · regional, not allelic
Overall
CADD	17.78	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 0.0176% South Asian · 16/91,034 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00889%

Overall 0.00105% 17/1,613,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,690
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Phe174Val
Coding: c.520T>G
MANE Select: NM_001673
dbSNP: rs560439034
Type: single nucleotide variant
Location: chr7:97859366 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36 · 3 PDB
Residue 174: the glutamine amidotransferase type-2 domain

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-phe174val (accessed [today's date]).

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