Is MTTP p.Asn404Ser (c.1211A>G) pathogenic?

MTTP p.Asn404Ser (c.1211A>G) is classified Conflicting classifications of pathogenicity in MTTP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-16). AlphaMissense: likely benign (0.056); Ultra-rare (popmax 0.0467%, afr).

How common is MTTP p.Asn404Ser (c.1211A>G) in the general population?

MTTP p.Asn404Ser (c.1211A>G) is ultra-rare (popmax 0.0467%, afr) (gnomAD).

What do computational predictors say about MTTP p.Asn404Ser (c.1211A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

MTTP p.Asn404Ser

c.1211A>G · rs150671886 · VCV2193516

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.50	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	GERP 0.05
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	11.09	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 0.0467% African / African-American · 35/75,020 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00886% 143/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0467%	2,143
East Asian	0.0245%	4,078
South Asian	0.00988%	10,120
European (non-Finnish)	0.00687%	14,565
Admixed American	0.00667%	14,999
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00156%	64,006

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: MTTP
Protein: p.Asn404Ser
Coding: c.1211A>G
MANE Select: NM_001386140
dbSNP: rs150671886
Type: single nucleotide variant
Location: chr4:99600708 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB
Residue 404: the vitellogenin domain

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

Similar variants

MTTP p.Asn404= Likely benign ★ same residue
MTTP c.1067+1G>C Likely pathogenic ★★ same type
MTTP c.1236+1G>A Pathogenic/Likely pathogenic ★★ same type
MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ same type
MTTP c.1867+1G>A Pathogenic ★★ same type
MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same type
MTTP c.1868-2A>G Likely pathogenic ★★ same type
MTTP c.2342+1G>A Pathogenic ★★ 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/mttp-p-asn404ser (accessed [today's date]).

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