Is DNAI7 p.Thr121Met (c.362C>T) pathogenic?

DNAI7 p.Thr121Met (c.362C>T) is classified Uncertain significance in DNAI7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.302); Ultra-rare (popmax 0.0496%, mid).

How common is DNAI7 p.Thr121Met (c.362C>T) in the general population?

DNAI7 p.Thr121Met (c.362C>T) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about DNAI7 p.Thr121Met (c.362C>T)?

AlphaMissense predicts likely benign (score 0.302) — an in-silico prediction, not a clinical call.

DNAI7 p.Thr121Met

c.362C>T · VCV4242982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.302 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.302	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -9.95	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 87 kb · p 0.044 · regional, not allelic
Overall
CADD	28.3	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T115M vs ClinVar T121M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0496% Middle Eastern · 3/6,052 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00385% 62/1,610,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
African / African-American	0.0441%	2,269
Remaining individualsnot grpmax-eligible	0.00962%	10,392
East Asian	0.00672%	14,886
Finnishnot grpmax-eligible	0.00156%	63,984
European (non-Finnish)	0.00127%	78,574
South Asian	0.00111%	90,436

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: DNAI7
Protein: p.Thr121Met
Coding: c.362C>T
MANE Select: NM_018272
Type: single nucleotide variant
Location: chr12:25154395 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01 · 1 PDB

Full DNAI7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI7 c.300+1G>A Uncertain significance ★ same type
DNAI7 p.Ala570Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Ala65Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Arg235Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg311Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg348Gln Uncertain significance ★ ⚠ same type
DNAI7 p.Arg39Cys Uncertain significance ★ ⚠ same type
DNAI7 p.Arg54Gln 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/dnai7-p-thr121met (accessed [today's date]).

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