Is NMUR2 p.Phe271Leu (c.813T>G) pathogenic?

NMUR2 p.Phe271Leu (c.813T>G) is classified Uncertain significance in NMUR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.6147); Ultra-rare (popmax 0.0134%, eas).

How common is NMUR2 p.Phe271Leu (c.813T>G) in the general population?

NMUR2 p.Phe271Leu (c.813T>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about NMUR2 p.Phe271Leu (c.813T>G)?

AlphaMissense predicts likely pathogenic (score 0.6147) — an in-silico prediction, not a clinical call.

NMUR2 p.Phe271Leu

c.813T>G · rs551355179 · VCV2522698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6147 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6147	likely pathogenic
REVEL	0.138	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP 0.77, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 13 kb · p 0.37 · regional, not allelic
Overall
CADD	16.56	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 0.0134% East Asian · 6/44,858 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,613,272 alleles · ultra-rare exomes 5/1,461,230 · genomes 2/152,042 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,476
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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: NMUR2
Protein: p.Phe271Leu
Coding: c.813T>G
MANE Select: NM_020167
dbSNP: rs551355179
Type: single nucleotide variant
Location: chr5:152395583 (GRCh38)
Gene constraint: LOEUF 1.327 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.92 · 3 PDB
Residue 271: an α-helix

Full NMUR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMUR2 p.Phe271Ser Uncertain significance ★ ⚠ same residue
NMUR2 p.Ala124Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala132Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala147Thr Uncertain significance ★ same type
NMUR2 p.Ala154Val Uncertain significance ★ ⚠ same type
NMUR2 p.Ala395Glu Uncertain significance ★ ⚠ same type
NMUR2 p.Arg108His Uncertain significance ★ ⚠ same type
NMUR2 p.Arg153Leu 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/nmur2-p-phe271leu (accessed [today's date]).

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