Is MAN2B2 p.Ile210Phe (c.628A>T) pathogenic?

MAN2B2 p.Ile210Phe (c.628A>T) is classified Benign in MAN2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2981); Low-frequency (popmax 3.12%, afr).

How common is MAN2B2 p.Ile210Phe (c.628A>T) in the general population?

MAN2B2 p.Ile210Phe (c.628A>T) is low-frequency (popmax 3.12%, afr) (gnomAD).

What do computational predictors say about MAN2B2 p.Ile210Phe (c.628A>T)?

AlphaMissense predicts likely benign (score 0.2981) — an in-silico prediction, not a clinical call.

MAN2B2 p.Ile210Phe

c.628A>T · VCV4689158

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2981 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.12%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2981	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -1.4
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.14 · regional, not allelic
Overall
CADD	14.89	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 3.12% African / African-American · 2,342/75,050 alleles

Filtering AF 3.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.97%

Overall 0.174% 2,802/1,614,178 alleles · low-frequency exomes 1,511/1,461,862 · genomes 1,291/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.12%	32
Remaining individualsnot grpmax-eligible	0.29%	345
Middle Eastern	0.198%	505
Admixed American	0.197%	509
South Asian	0.0132%	7,590
European (non-Finnish)	0.0116%	8,613

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: MAN2B2
Protein: p.Ile210Phe
Coding: c.628A>T
MANE Select: NM_015274
Type: single nucleotide variant
Location: chr4:6589108 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.55

Full MAN2B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAN2B2 p.Gln615Ter Pathogenic/Likely pathogenic ★★ same type
MAN2B2 p.Trp284Ter Pathogenic/Likely pathogenic ★★ same type
MAN2B2 p.Ala155Thr Uncertain significance ★★ ⚠ same type
MAN2B2 p.Ala868Thr Uncertain significance ★★ ⚠ same type
MAN2B2 p.Arg411His Uncertain significance ★★ ⚠ same type
MAN2B2 p.Arg447Gly Uncertain significance ★★ ⚠ same type
MAN2B2 p.Arg683Gln Uncertain significance ★★ ⚠ same type
MAN2B2 p.Arg975Ser 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/man2b2-p-ile210phe (accessed [today's date]).

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