Is NDUFA10 p.Pro103= (c.309C>T) pathogenic?

NDUFA10 p.Pro103= (c.309C>T) is classified Likely benign in NDUFA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-17). Ultra-rare (popmax 0.0133%, amr).

How common is NDUFA10 p.Pro103= (c.309C>T) in the general population?

NDUFA10 p.Pro103= (c.309C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

NDUFA10 p.Pro103=

c.309C>T · rs753946240 · VCV2037035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -2.8, phastCons 0.98
Overall
CADD	3.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,004 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00062% 10/1,614,034 alleles · ultra-rare exomes 7/1,461,888 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
European (non-Finnish)	0.000169%	590,023

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: NDUFA10
Protein: p.Pro103=
Coding: c.309C>T
MANE Select: NM_004544
dbSNP: rs753946240
Type: single nucleotide variant
Location: chr2:240021348 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.79 · 6 PDB

Full NDUFA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NDUFA10 p.Arg139Cys Likely pathogenic ★★ same type
NDUFA10 c.999+4A>G Uncertain significance ★★ same type
NDUFA10 p.Ala105Thr Uncertain significance ★★ ⚠ same type
NDUFA10 p.Ala232Pro Uncertain significance ★★ ⚠ same type
NDUFA10 p.Arg289Cys Uncertain significance ★★ ⚠ same type
NDUFA10 p.Arg326Cys Uncertain significance ★★ ⚠ same type
NDUFA10 p.Arg337His Uncertain significance ★★ ⚠ same type
NDUFA10 p.Arg37Cys 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/ndufa10-p-pro103 (accessed [today's date]).

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