Is NOD1 p.Ala554Val (c.1661C>T) pathogenic?

NOD1 p.Ala554Val (c.1661C>T) is classified Likely benign in NOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0849); Ultra-rare (popmax 0.0494%, mid).

How common is NOD1 p.Ala554Val (c.1661C>T) in the general population?

NOD1 p.Ala554Val (c.1661C>T) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

What do computational predictors say about NOD1 p.Ala554Val (c.1661C>T)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

NOD1 p.Ala554Val

c.1661C>T · rs5743344 · VCV3201008

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.68	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 -0.88	GERP -3.6
Regional constraint	o/e 1.00	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	0.977	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 0.0494% Middle Eastern · 3/6,076 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.0134% 216/1,613,562 alleles · ultra-rare exomes 191/1,461,394 · genomes 25/152,168 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.345%	290
Middle Easterngrpmax	0.0494%	2,025
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Admixed American	0.0167%	6,000
East Asian	0.00891%	11,219
European (non-Finnish)	0.00619%	16,164
African / African-American	0.00267%	37,465
South Asian	0.0011%	91,090

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NOD1
Protein: p.Ala554Val
Coding: c.1661C>T
MANE Select: NM_006092
dbSNP: rs5743344
Type: single nucleotide variant
Location: chr7:30451756 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.87 · 6 PDB

Full NOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOD1 p.Ala833Thr Uncertain significance ★★ ⚠ same type
NOD1 p.Ser16Phe Uncertain significance ★★ ⚠ same type
NOD1 p.Arg214Gln Likely benign ★★ same type
NOD1 p.Ala148Gly Uncertain significance ★ ⚠ same type
NOD1 p.Ala279Ser Uncertain significance ★ ⚠ same type
NOD1 p.Ala315Thr Uncertain significance ★ ⚠ same type
NOD1 p.Ala467Thr Uncertain significance ★ ⚠ same type
NOD1 p.Ala522Thr 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/nod1-p-ala554val (accessed [today's date]).

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